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Sample records for acid dota derivatives

  1. Biotin derivatives carrying two chelating DOTA units. Synthesis, in vitro evaluation of biotinidases resistance, avidin binding, and radiolabeling tests

    OpenAIRE

    Pratesi, Alessandro; Bucelli, Francesca; Mori, Ilaria; Chinol, Marco; Verdoliva, Antonio; Paganelli, Giovanni; Rivieccio, Vincenzo; Gariboldi, Lucia; Ginanneschi, Mauro

    2010-01-01

    The synthesis of four biotin derivatives carrying two DOTA moieties for each ligand (BisDOTA set) is reported, for increasing radiation/dose ratio and improving efficiency in the pretargeted avidin-biotin radioimmunotherapy. The biotin-containing scaffold of two BisDOTA was similar to the mono-DOTA derivative previously described. Then the scaffold was elongated by trifunctionalized spacers of different length and conjugated with one of the COOH groups of two DOTA. Two others were prepared st...

  2. DOTA-PESIN, a DOTA-conjugated bombesin derivative designed for the imaging and targeted radionuclide treatment of bombesin receptor-positive tumours

    International Nuclear Information System (INIS)

    We aimed at designing and developing a novel bombesin analogue, DOTA-PEG4-BN(7-14) (DOTA-PESIN), with the goal of labelling it with 67/68Ga and 177Lu for diagnosis and radionuclide therapy of prostate and other human cancers overexpressing bombesin receptors. The 8-amino acid peptide bombesin (7-14) was coupled to the macrocyclic chelator DOTA via the spacer 15-amino-4,7,10,13-tetraoxapentadecanoic acid (PEG4). The conjugate was complexed with Ga(III) and Lu(III) salts. The GRP receptor affinity and the bombesin receptor subtype profile were determined in human tumour specimens expressing the three bombesin receptor subtypes. Internalisation and efflux studies were performed with the human GRP receptor cell line PC-3. Xenografted nude mice were used for biodistribution. [GaIII/LuIII]-DOTA-PESIN showed good affinity to GRP and neuromedin B receptors but no affinity to BB3. [67Ga/177Lu]-DOTA-PESIN internalised rapidly into PC-3 cells whereas the efflux from PC-3 cells was relatively slow. In vivo experiments showed a high and specific tumour uptake and good retention of [67Ga/177Lu]-DOTA-PESIN. [67Ga/177Lu]-DOTA-PESIN highly accumulated in GRP receptor-expressing mouse pancreas. The uptake specificity was demonstrated by blocking tumour uptake and pancreas uptake. Fast clearance was found from blood and all non-target organs except the kidneys. High tumour-to-normal tissue ratios were achieved, which increased with time. PET imaging with [68Ga]-DOTA-PESIN was successful in visualising the tumour at 1 h post injection. Planar scintigraphic imaging showed that the 177Lu-labelled peptide remained in the tumour even 3 days post injection. The newly designed ligands have high potential with regard to PET and SPECT imaging with 68/67Ga and targeted radionuclide therapy with 177Lu. (orig.)

  3. DOTA-PESIN, a DOTA-conjugated bombesin derivative designed for the imaging and targeted radionuclide treatment of bombesin receptor-positive tumours

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hanwen; Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry, Department of Radiology, Basel (Switzerland); Schuhmacher, Jochen; Eisenhut, Michael [German Cancer Research Centre, Department of Radiopharmaceutical Chemistry, Heidelberg (Germany); Waser, Beatrice; Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, P.O. Box 62, Berne (Switzerland); Wild, Damian [University Hospital, Clinic and Institute of Nuclear Medicine, Department of Radiology, Basel (Switzerland)

    2007-08-15

    We aimed at designing and developing a novel bombesin analogue, DOTA-PEG{sub 4}-BN(7-14) (DOTA-PESIN), with the goal of labelling it with {sup 67/68}Ga and {sup 177}Lu for diagnosis and radionuclide therapy of prostate and other human cancers overexpressing bombesin receptors. The 8-amino acid peptide bombesin (7-14) was coupled to the macrocyclic chelator DOTA via the spacer 15-amino-4,7,10,13-tetraoxapentadecanoic acid (PEG{sub 4}). The conjugate was complexed with Ga(III) and Lu(III) salts. The GRP receptor affinity and the bombesin receptor subtype profile were determined in human tumour specimens expressing the three bombesin receptor subtypes. Internalisation and efflux studies were performed with the human GRP receptor cell line PC-3. Xenografted nude mice were used for biodistribution. [Ga{sup III}/Lu{sup III}]-DOTA-PESIN showed good affinity to GRP and neuromedin B receptors but no affinity to BB3. [{sup 67}Ga/{sup 177}Lu]-DOTA-PESIN internalised rapidly into PC-3 cells whereas the efflux from PC-3 cells was relatively slow. In vivo experiments showed a high and specific tumour uptake and good retention of [{sup 67}Ga/{sup 177}Lu]-DOTA-PESIN. [{sup 67}Ga/{sup 177}Lu]-DOTA-PESIN highly accumulated in GRP receptor-expressing mouse pancreas. The uptake specificity was demonstrated by blocking tumour uptake and pancreas uptake. Fast clearance was found from blood and all non-target organs except the kidneys. High tumour-to-normal tissue ratios were achieved, which increased with time. PET imaging with [{sup 68}Ga]-DOTA-PESIN was successful in visualising the tumour at 1 h post injection. Planar scintigraphic imaging showed that the {sup 177}Lu-labelled peptide remained in the tumour even 3 days post injection. The newly designed ligands have high potential with regard to PET and SPECT imaging with {sup 68/67}Ga and targeted radionuclide therapy with {sup 177}Lu. (orig.)

  4. Synthesis and Characterization of DOTA-(amide)4 Derivatives: Equilibrium and Kinetic Behavior of Their Lanthanide(III) Complexes

    OpenAIRE

    Pasha, Azhar; Tircsó, Gyula; Benyó, Enikő Tircsóné; Brücher, Ernő; Sherry, A. Dean

    2007-01-01

    Lanthanide complexes of tetraamide derivatives of DOTA are of interest today because of their application as chemical exchange saturation transfer (CEST) agents for magnetic resonance imaging (MRI). The protonation constants of some simple tetraamide derivatives of DOTA and the stability constants of the complexes formed with some endogenous metal ions, namely Mg2+, Ca2+, Cu2+, Zn2+, and lanthanide(III) ions, have been studied. These complexes were found to be considerably less stable than th...

  5. Isomerism in benzyl-DOTA derived bifunctional chelators: implications for molecular imaging.

    Science.gov (United States)

    Payne, Katherine M; Woods, Mark

    2015-02-18

    The bifunctional chelator IB-DOTA has found use in a range of biomedical applications given its ability to chelate many metal ions, but in particular the lanthanide(III) ions. Gd(3+) in particular is of interest in the development of new molecular imaging agents for MRI and is highly suitable for chelation by IB-DOTA. Given the long-term instability of the aryl isothiocyanate functional group we have used the more stable nitro derivative (NB-DOTA) to conduct a follow-up study of some of our previous work on the coordination chemistry of chelates of these BFCs. Using a combination of NMR and HPLC to study the Eu(3+) and Yb(3+) chelates of NB-DOTA, we have demonstrated that this ligand will produce two discrete regioisomeric chelates at the point at which the metal ion is introduced into the BFC. These regioisomers are defined by the position of the benzylic substituent on the macrocyclic ring: adopting an equatorial position either at the corner or the side of the [3333] ring conformation. These regioisomers are incapable of interconversion and are distinct, separate structures with different SAP/TSAP ratios. The side isomer exhibits an increased population of the TSAP isomer, pointing to more rapid water exchange kinetics in this regioisomer. This has potential ramifications for the use of these two regioisomers of Gd(3+)-BFC chelates in MRI applications. We have also found that, remarkably, there is little or no freedom of rotation about the first single bond extending from the macrocyclic ring to the benzylic substituent. Since this is the linkage through which the chelate is conjugated to the remainder of the molecular imaging probe, this result implies that there may be reduced local rotation of the Gd(3+) chelate within a molecular imaging probe. This implies that this type of BFC could exhibit higher relaxivities than other types of BFC.

  6. Evaluation of maleimide derivative of DOTA for site-specific labeling of recombinant affibody molecules.

    Science.gov (United States)

    Ahlgren, Sara; Orlova, Anna; Rosik, Daniel; Sandström, Mattias; Sjöberg, Anna; Baastrup, Barbro; Widmark, Olof; Fant, Gunilla; Feldwisch, Joachim; Tolmachev, Vladimir

    2008-01-01

    Affibody molecules are a new class of small (7 kDa) scaffold affinity proteins, which demonstrate promising properties as agents for in vivo radionuclide targeting. The Affibody scaffold is cysteine-free and therefore independent of disulfide bonds. Thus, a single thiol group can be engineered into the protein by introduction of one cysteine. Coupling of thiol-reactive bifunctional chelators can enable site-specific labeling of recombinantly produced Affibody molecules. In this study, the use of 1,4,7,10-tetraazacyclododecane-1,4,7-tris-acetic acid-10-maleimidoethylacetamide (MMA-DOTA) for 111 In-labeling of anti-HER2 Affibody molecules His 6-Z HER2:342-Cys and Z HER2:2395-Cys has been evaluated. The introduction of a cysteine residue did not affect the affinity of the proteins, which was 29 pM for His 6-Z HER2:342-Cys and 27 pM for Z HER2:2395-Cys, comparable with 22 pM for the parental Z HER2:342. MMA-DOTA was conjugated to DTT-reduced Affibody molecules with a coupling efficiency of 93% using a 1:1 molar ratio of chelator to protein. The conjugates were labeled with 111 In to a specific radioactivity of up to 7 GBq/mmol, with preserved binding for the target HER2. In vivo, the non-His-tagged variant 111 In-[MMA-DOTA-Cys61]-Z HER2:2395-Cys demonstrated appreciably lower liver uptake than its His-tag-containing counterpart. In mice bearing HER2-expressing LS174T xenografts, 111 In-[MMA-DOTA-Cys61]-Z HER2:2395-Cys showed specific and rapid tumor localization, and rapid clearance from blood and nonspecific compartments, leading to a tumor-to-blood-ratio of 18 +/- 8 already 1 h p.i. Four hours p.i., the tumor-to-blood ratio was 138 +/- 8. Xenografts were clearly visualized already 1 h p.i. PMID:18163536

  7. Mechanism and energetics for complexation of 90Y with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a model for cancer radioimmunotherapy

    International Nuclear Information System (INIS)

    A promising cancer therapy involves the use of the macrocyclic polyaminoacetate DOTA (1,4,6,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) attached to a tumor-targeting antibody complexed with the β emitter 90Y3+. However, incorporation of the 90Y into the DOTA conjugate is too slow. To identify the origins of this problem, ab initio quantum chemistry methods (B3LYP/:ACVP* and HF/LACVP*) were used to predict structures and energetics. The authors find that the initial complex YH2(DOTA)+ is 4-coordinate (the four equivalent carboxylate oxygens), which transforms to YH(DOTA) (5-coordinate with one ring N and four carboxylate oxygens), and finally to Y(DOTA)-, which is 8-coordinate (four oxygens and four nitrogens). The rate-determining step is the conversion of YH(DOTA) to Y(DOTA)-, which was calculated to have an activation free energy (aqueous phase) of 8.4 kcal/mol, in agreement with experimental results (8.1--9.3 kcal/mol) for various metals to DOTA [Kumar, K.; Tweedle, M.F. Inorg. Chem. 1993, 32, 4193--4199; Wu, S.L.; Horrocks, W.D., Jr., Inorg. Chem. 1995, 34, 3724--2732]. On the basis of this mechanism the authors propose a modified chelate, DO3AlPr, which has calculated at a much faster rate of incorporation

  8. DOTA-functionalized polylysine: a high number of DOTA chelates positively influences the biodistribution of enzymatic conjugated anti-tumor antibody chCE7agl.

    Directory of Open Access Journals (Sweden)

    Jürgen Grünberg

    Full Text Available Site-specific enzymatic reactions with microbial transglutaminase (mTGase lead to a homogenous species of immunoconjugates with a defined ligand/antibody ratio. In the present study, we have investigated the influence of different numbers of 1,4,7,10-tetraazacyclododecane-N-N'-N''-N'''-tetraacetic acid (DOTA chelats coupled to a decalysine backbone on the in vivo behavior of the chimeric monoclonal anti-L1CAM antibody chCE7agl. The enzymatic conjugation of (DOTA1-decalysine, (DOTA3-decalysine or (DOTA5-decalysine to the antibody heavy chain (via Gln295/297 gave rise to immunoconjugates containing two, six or ten DOTA moieties respectively. Radiolabeling of the immunoconjugates with (177Lu yielded specific activities of approximately 70 MBq/mg, 400 MBq/mg and 700 MBq/mg with increasing numbers of DOTA chelates. Biodistribution experiments in SKOV3ip human ovarian cancer cell xenografts demonstrated a high and specific accumulation of radioactivity at the tumor site for all antibody derivatives with a maximal tumor accumulation of 43.6±4.3% ID/g at 24 h for chCE7agl-[(DOTA-decalysine]2, 30.6±12.0% ID/g at 24 h for chCE7agl-[(DOTA3-decalysine]2 and 49.9±3.1% ID/g at 48 h for chCE7agl-[(DOTA5-decalysine]2. The rapid elimination from the blood of chCE7agl-[(DOTA-decalysine]2 (1.0±0.1% ID/g at 24 h is associated with a high liver accumulation (23.2±4.6% ID/g at 24 h. This behavior changed depending on the numbers of DOTA moieties coupled to the decalysine peptide with a slower blood clearance (5.1±1.0 (DOTA3 versus 11.7±1.4% ID/g (DOTA5, p<0.005 at 24 h and lower radioactivity levels in the liver (21.4±3.4 (DOTA3 versus 5.8±0.7 (DOTA5, p<0.005 at 24 h. We conclude that the site-specific and stoichiometric uniform conjugation of the highly DOTA-substituted decalysine ((DOTA5-decalysine to an anti-tumor antibody leads to the formation of immunoconjugates with high specific activity and excellent in vivo behavior and is a valuable option for

  9. Application of new bifunctional chelator DOTA and its derivatives in the metal radionuclide labeled compounds%新型双功能螯合剂DOTA及其衍生物在金属核素标记中的应用进展

    Institute of Scientific and Technical Information of China (English)

    陈飞; 蒋孟军; 朱宝

    2016-01-01

    DOTA及其衍生物是应用最为广泛的新型双功能螯合剂之一.DOTA及其衍生物不仅具有成熟的合成工艺路线,还具有良好的配位和螯合能力,DOTA-多肽分子探针作为MRI对比剂、核素靶向显像剂和放射性药物在生物医学领域被广泛应用.笔者对DOTA双功能螯合剂的种类、DOTA-多肽标记前体的合成和DOTA-多肽金属配合物的应用进行综述.%DOTA and its derivatives are most widely uscd novel bifunctional chelators.They have not only mature synthesis route,but also good coordination and chelating ability.Therefore,DOTA metal complexes of DOTA-peptide conjugates are increasingly used as MRI contrast agents,radionuclide targeted imaging agents and therapeutic radiopharmaceuticals in the biomedical field.This review covers the bifunctional derivatives of DOTA,the synthesis of DOTA-peptide conjugates,and the applications of DOTA-peptide conjugate metal complexes.

  10. Scandium(III) complexes of monophosphorus acid DOTA analogues: a thermodynamic and radiolabelling study with (44)Sc from cyclotron and from a (44)Ti/(44)Sc generator.

    Science.gov (United States)

    Kerdjoudj, R; Pniok, M; Alliot, C; Kubíček, V; Havlíčková, J; Rösch, F; Hermann, P; Huclier-Markai, S

    2016-01-28

    The complexation ability of DOTA analogs bearing one methylenephosphonic (DO3AP) or methylenephosphinic (DO3AP(PrA) and DO3AP(ABn)) acid pendant arm toward scandium was evaluated. Stability constants of their scandium(iii) complexes were determined by potentiometry combined with (45)Sc NMR spectroscopy. The stability constants of the monophosphinate analogues are somewhat lower than that of the Sc-DOTA complex. The phosphorus acid moiety interacts with trivalent scandium even in very acidic solutions forming out-of-cage complexes; the strong affinity of the phosphonate group to Sc(iii) precludes stability constant determination of the Sc-DO3AP complex. These results were compared with those obtained by the free-ion selective radiotracer extraction (FISRE) method which is suitable for trace concentrations. FISRE underestimated the stability constants but their relative order was preserved. Nonetheless, as this method is experimentally simple, it is suitable for a quick relative comparison of stability constant values under trace concentrations. Radiolabelling of the ligands with (44)Sc was performed using the radioisotope from two sources, a (44)Ti/(44)Sc generator and (44m)Sc/(44)Sc from a cyclotron. The best radiolabelling conditions for the ligands were pH = 4, 70 °C and 20 min which were, however, not superior to those of the parent DOTA. Nonetheless, in vitro behaviour of the Sc(iii) complexes in the presence of hydroxyapatite and rat serum showed sufficient stability of (44)Sc complexes of these ligands for in vivo applications. PET images and ex vivo biodistribution of the (44)Sc-DO3AP complex performed on healthy Wistar male rats showed no specific bone uptake and rapid clearance through urine. PMID:26675416

  11. Influence of biological assay conditions on stability assessment of radiometal-labelled peptides exemplified using a 177Lu-DOTA-minigastrin derivative

    International Nuclear Information System (INIS)

    Introduction: Lack of correlation between in vitro and in vivo stability is a general problem for the development of radiopeptides especially in the case of minigastrin derivatives for therapeutic applications. In this study, we compared the influence of experimental conditions on radiopeptide stability results in vitro using a model Minigastrin (MG) analogue labelled with Lu-177. Additionally, we attempted to characterize the main serum enzymatic cleavage sites by matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) analysis. Methods: In vitro stability of a DOTA-minigastrin derivative (177Lu-DOTA-His-His-Glu-Ala-Tyr-Gly-Trp-NIe-Asp-Phe-NH2) was tested in serum, rat tissue homogenates and two different standardised enzymatic mixtures. Quantification of the metabolised radiopeptides at different time intervals was performed using reversed-phase high-performance liquid chromatography (RP-HPLC). Metabolites were characterised by MALDI-TOF-MS. Urine was collected after 15 min p.i. into the mice and compared with in vitro metabolites by RP-HPLC. Results: Faster degradation of the radiopeptide was found in blood in comparison with plasma and serum incubation and in components from rats faster than from human origin. Fast degradation was observed in kidney and liver homogenates as well as in standardised enzymatic mixtures, also revealing variations in the metabolic profile. In urine, no intact peptide was detected already 5 min post injection. MALDI-TOF-MS revealed major cleavage sites at the carboxy terminus of the peptide. Conclusion: Very variable results may be found when different kind of incubation media for testing radiopeptide stabilities is used. Serum incubation studies may overestimate stability; therefore, results should be interpreted with care and combined with alternative in vitro and in vivo investigations.

  12. Influence of biological assay conditions on stability assessment of radiometal-labelled peptides exemplified using a {sup 177}Lu-DOTA-minigastrin derivative

    Energy Technology Data Exchange (ETDEWEB)

    Ocak, Meltem [Clinical Department of Nuclear Medicine, Medical University Innsbruck, A-6020, Innsbruck (Austria); Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul University, 34116, Istanbul (Turkey); Helbok, Anna; Guggenberg, Elisabeth von [Clinical Department of Nuclear Medicine, Medical University Innsbruck, A-6020, Innsbruck (Austria); Ozsoy, Y. [Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul University, 34116, Istanbul (Turkey); Kabasakal, Levent [Department of Nuclear Medicine, Cerrahpasa Medical Faculty, 34098, Istanbul (Turkey); Kremser, Leopold [Division of Clinical Biochemistry, Protein Micro-Analysis Facility, Biocenter, Medical University Innsbruck, A-6020, Innsbruck (Austria); Decristoforo, Clemens, E-mail: clemens.decristoforo@uki.a [Clinical Department of Nuclear Medicine, Medical University Innsbruck, A-6020, Innsbruck (Austria)

    2011-02-15

    Introduction: Lack of correlation between in vitro and in vivo stability is a general problem for the development of radiopeptides especially in the case of minigastrin derivatives for therapeutic applications. In this study, we compared the influence of experimental conditions on radiopeptide stability results in vitro using a model Minigastrin (MG) analogue labelled with Lu-177. Additionally, we attempted to characterize the main serum enzymatic cleavage sites by matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) analysis. Methods: In vitro stability of a DOTA-minigastrin derivative ({sup 177}Lu-DOTA-His-His-Glu-Ala-Tyr-Gly-Trp-NIe-Asp-Phe-NH{sub 2}) was tested in serum, rat tissue homogenates and two different standardised enzymatic mixtures. Quantification of the metabolised radiopeptides at different time intervals was performed using reversed-phase high-performance liquid chromatography (RP-HPLC). Metabolites were characterised by MALDI-TOF-MS. Urine was collected after 15 min p.i. into the mice and compared with in vitro metabolites by RP-HPLC. Results: Faster degradation of the radiopeptide was found in blood in comparison with plasma and serum incubation and in components from rats faster than from human origin. Fast degradation was observed in kidney and liver homogenates as well as in standardised enzymatic mixtures, also revealing variations in the metabolic profile. In urine, no intact peptide was detected already 5 min post injection. MALDI-TOF-MS revealed major cleavage sites at the carboxy terminus of the peptide. Conclusion: Very variable results may be found when different kind of incubation media for testing radiopeptide stabilities is used. Serum incubation studies may overestimate stability; therefore, results should be interpreted with care and combined with alternative in vitro and in vivo investigations.

  13. Associating a negatively charged GdDOTA-derivative to the Pittsburgh compound B for targeting Aβ amyloid aggregates.

    Science.gov (United States)

    Martins, André F; Oliveira, Alexandre C; Morfin, Jean-François; Laurents, Douglas V; Tóth, Éva; Geraldes, Carlos F G C

    2016-03-01

    We have conjugated the tetraazacyclododecane-tetraacetate (DOTA) chelator to Pittsburgh compound B (PiB) forming negatively charged lanthanide complexes, Ln(L4), with targeting capabilities towards aggregated amyloid peptides. The amphiphilic Gd(L4) chelate undergoes micellar aggregation in aqueous solution, with a critical micellar concentration of 0.68 mM, lower than those for the neutral complexes of similar structure. A variable temperature (17)O NMR and NMRD study allowed the assessment of the water exchange rate, k ex (298) = 9.7 × 10(6) s(-1), about the double of GdDOTA, and for the description of the rotational dynamics for both the monomeric and the micellar forms of Gd(L4). With respect to the analogous neutral complexes, the negative charge induces a significant rigidity of the micelles formed, which is reflected by slower and more restricted local motion of the Gd(3+) centers as evidenced by higher relaxivities at 20-60 MHz. Surface Plasmon Resonance results indicate that the charge does not affect significantly the binding strength to Aβ1-40 [K d = 194 ± 11 μM for La(L4)], but it does enhance the affinity constant to human serum albumin [K a = 6530 ± 68 M(-1) for Gd(L4)], as compared to neutral counterparts. Protein-based NMR points to interaction of Gd(L4) with Aβ1-40 in the monomer state as well, in contrast to neutral complexes interacting only with the aggregated form. Circular dichroism spectroscopy monitored time- and temperature-dependent changes of the Aβ1-40 secondary structure, indicating that Gd(L4) stabilizes the random coil relative to the α-helix and β-sheet. TEM images confirm that the Gd(L4) complex reduces the formation of aggregated fibrils. PMID:26613605

  14. Positron emission tomography study on pancreatic somatostatin receptors in normal and diabetic rats with 68Ga-DOTA-octreotide: A potential PET tracer for beta cell mass measurement

    International Nuclear Information System (INIS)

    Highlights: •PET images showed high uptake of 68Ga-DOTA-octreotide in the normal pancreas. •68Ga-DOTA-octreotide specifically binds to somatostatin receptors in the pancreas. •The pancreatic uptake of 68Ga-DOTA-octreotide was decreased in the diabetic rats. •68Ga-DOTA-octreotide could be a candidate PET probe to measure the beta cell mass. -- Abstract: Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, and the loss or dysfunction of pancreatic beta cells has been reported before the appearance of clinical symptoms and hyperglycemia. To evaluate beta cell mass (BCM) for improving the detection and treatment of DM at earlier stages, we focused on somatostatin receptors that are highly expressed in the pancreatic beta cells, and developed a positron emission tomography (PET) probe derived from octreotide, a metabolically stable somatostatin analog. Octreotide was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a chelating agent, and labeled with 68Gallium (68Ga). After intravenous injection of 68Ga-DOTA-octreotide, a 90-min emission scan of the abdomen was performed in normal and DM model rats. The PET studies showed that 68Ga-DOTA-octreotide radioactivity was highly accumulated in the pancreas of normal rats and that the pancreatic accumulation was significantly reduced in the rats administered with an excess amount of unlabeled octreotide or after treatment with streptozotocin, which was used for the chemical induction of DM in rats. These results were in good agreement with the ex vivo biodistribution data. These results indicated that the pancreatic accumulation of 68Ga-DOTA-octreotide represented specific binding to the somatostatin receptors and reflected BCM. Therefore, PET imaging with 68Ga-DOTA-octreotide could be a potential tool for evaluating BCM

  15. The chemical fate of 212Bi-DOTA formed by β- decay of 212Pb(DOTA)2-

    International Nuclear Information System (INIS)

    The increasing use of inert metal complexes in radioimmunotherapy prompted us to explore the potential use of 212Pb chelates. Herein, we report a study of the chemical fate of the 212Bi-DOTA complex formed by β- decay of 212Pb(DOTA)2-(H4DOTA = 1,4,7,10-tetraazacyclododecanetetraacetic acid). To assure that both parent and daughter complexes were thermally stable, kinetic studies were performed with 203Pb(II) and 206Bi(III) which showed that both lead and bismuth complexes with DOTA undergo chemical exchange only very slowly in aqueous solution at pH 4-10. To investigate whether the complex ion which results from decay of 212Pb(DOTA)2- was intact and also stable, solutions initially containing only this ion were analyzed for amounts of DOTA-complexed and uncomplexed 212Bi after attaining transient equilibrium with 212Bi. The fraction of 212Bi radioactivity not complexed to DOTA, vide infra, was found to be 36±2%. This value represents the fraction of breakup of 212Bi(DOTA)- formed from β- decay of the parent complex. By considering the various extranuclear processes responsible for kinetic and electronic excitation of the 212Bi daughter, break-up of the 212Bi-DOTA complex is ascribed to the internal conversion of γ-rays emitted by the excited 212Bi nuclide. (orig.)

  16. DOTA-Tyr3-octreotate labelled with 177Lu and 131I. A comparative evaluation

    International Nuclear Information System (INIS)

    The chemical structure of somatostatin receptor ligand 1,4,7,10-tetraazacyclododecane- N,N',N',N'''-tetraacetic acid-Tyr3-octreotate (DOTA-Tyr3-TATE), provides the means for radiolabelling with halogen, by electrophilic substitution, to the Tyr3 residue and with metal, by a coordination mechanism, to the DOTA chelator. In this study, the DOTA-Tyr3-TATE was radiolabelled with 177Lu and 131I of high radiochemical purity and specific activity. The in vitro study regarding the competitive and the saturation binding assays were performed using rat brain cortex membrane. The IC50 value was determined as 4.74nM for natLu-DOTA-Tyr3-TATE and the Kd value was 142.8pM for 177Lu-DOTA-Tyr3-TATE. The biodistribution data of 177Lu-DOTA-Tyr3-TATE and DOTA-131I-Tyr3-TATE in HRS1 (hepato-colangiom carcinomas) tumour bearing rats, show that the 177Lu-DOTA-Tyr3-TATE is more stable and has better uptake than DOTA-131I-Tyr3-TATE. Furthermore, the competitive localization index of 177Lu- DOTA-Tyr3-TATE is three times higher than that obtained for DOTA-131I -Tyr3-TATE. The results of work based on comparative experiments suggest that 177Lu-DOTA-Tyr3- TATE could be an effective targeted radiotherapy agent of SSTR tumours. (author)

  17. Joint analysis of ESR lineshapes and 1H NMRD profiles of DOTA-Gd derivatives by means of the slow motion theory

    Science.gov (United States)

    Kruk, D.; Kowalewski, J.; Tipikin, D. S.; Freed, J. H.; Mościcki, M.; Mielczarek, A.; Port, M.

    2011-01-01

    The "Swedish slow motion theory" [Nilsson and Kowalewski, J. Magn. Reson. 146, 345 (2000)] applied so far to Nuclear Magnetic Relaxation Dispersion (NMRD) profiles for solutions of transition metal ion complexes has been extended to ESR spectral analysis, including in addition g-tensor anisotropy effects. The extended theory has been applied to interpret in a consistent way (within one set of parameters) NMRD profiles and ESR spectra at 95 and 237 GHz for two Gd(III) complexes denoted as P760 and P792 (hydrophilic derivatives of DOTA-Gd, with molecular masses of 5.6 and 6.5 kDa, respectively). The goal is to verify the applicability of the commonly used pseudorotational model of the transient zero field splitting (ZFS). According to this model the transient ZFS is described by a tensor of a constant amplitude, defined in its own principal axes system, which changes its orientation with respect to the laboratory frame according to the isotropic diffusion equation with a characteristic time constant (correlation time) reflecting the time scale of the distortional motion. This unified interpretation of the ESR and NMRD leads to reasonable agreement with the experimental data, indicating that the pseudorotational model indeed captures the essential features of the electron spin dynamics.

  18. Y-90-DOTA-hLL2: An Agent for Radioimmunotherapy of Non-Hodgkin's Lymphoma

    International Nuclear Information System (INIS)

    The goal of this work was to determine an optimal radioimmunotherapy agent for non-Hodgkin's lymphoma. We established the stability profile of yttrium-90-labeled humanized LL2 (hLL2) monoclonal antibody prepared with different chelating agents, and from these data estimated the improvement using the most stable yttrium-90 chelate-hLL2 complex. Methods: The complementary-determining region- (cdr)-grafted (humanized) anti-CD22 mAb, hLL2 (epratuzumab), was conjugated to derivatives of DTPA and 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA). The conjugates were labeled with Y-90 and tested against a 10,000-fold molar excess of free DTPA and against human serum. The conjugates were also labeled with Y-88 and compared for biodistribution in normal and lymphoma xenograft-bearing athymic mice. In vivo data were analyzed for uptake of yttrium in bone and washed bone when either the DOTA or the Mx-DTPA chelates were used, and dosimetry calculations were made for each. Results: Y-90-DOTA -mAb were stable to either DTPA or serum challenge. DTPA complexes of hLL2 lost 3-4% of Y-90 (days 1-4) and 10-15% thereafter. In vivo, stability differences showed lower Y-90 uptake in bone using DOTA. Absorbed doses per 37 MBq (1 mCi) Y-90-mAb were 3555 and 5405 cGy for bone, and 2664 and 4524 cGy for washed-bone for 90Y-DOTA-hLL2 and 90Y-MxDTPA-hLL2, respectively, amounting to 52% and 69.8% increases in absorbed radiation doses for bone and washed-bone when switching from a DOTA to a Mx-DTPA chelate. Conclusion: Y-90-hLL2 prepared with the DOTA chelate represents a preferred agent for RAIT of non-Hodgkin's lymphoma, with an in vivo model demonstrating a large reduction in bone-deposited yttrium, as compared to yttrium-90-hLL2 agents prepared with open-chain DTPA-type chelating agents. Dosimetry suggests that this will result in a substantial toxicological advantage for a DOTA-based hLL2 conjugate

  19. Preliminary Therapy Evaluation of (225)Ac-DOTA-c(RGDyK) Demonstrates that Cerenkov Radiation Derived from (225)Ac Daughter Decay Can Be Detected by Optical Imaging for In Vivo Tumor Visualization.

    Science.gov (United States)

    Pandya, Darpan N; Hantgan, Roy; Budzevich, Mikalai M; Kock, Nancy D; Morse, David L; Batista, Izadora; Mintz, Akiva; Li, King C; Wadas, Thaddeus J

    2016-01-01

    The theranostic potential of (225)Ac-based radiopharmaceuticals continues to increase as researchers seek innovative ways to harness the nuclear decay of this radioisotope for therapeutic and imaging applications. This communication describes the evaluation of (225)Ac-DOTA-c(RGDyK) in both biodistribution and Cerenkov luminescence imaging (CLI) studies. Initially, La-DOTA-c(RGDyK) was prepared as a non-radioactive surrogate to evaluate methodologies that would contribute to an optimized radiochemical synthetic strategy and estimate the radioactive conjugate's affinity for αvβ3, using surface plasmon resonance spectroscopy. Surface plasmon resonance spectroscopy studies revealed the IC50 and Ki of La-DOTA-c(RGDyK) to be 33 ± 13 nM and 26 ± 11 nM, respectively, and suggest that the complexation of the La(3+) ion to the conjugate did not significantly alter integrin binding. Furthermore, use of this surrogate allowed optimization of radiochemical synthesis strategies to prepare (225)Ac-DOTA-c(RGDyK) with high radiochemical purity and specific activity similar to other (225)Ac-based radiopharmaceuticals. This radiopharmaceutical was highly stable in vitro. In vivo biodistribution studies confirmed the radiotracer's ability to target αvβ3 integrin with specificity; specificity was detected in tumor-bearing animals using Cerenkov luminescence imaging. Furthermore, tumor growth control was achieved using non-toxic doses of the radiopharmaceutical in U87mg tumor-bearing nude mice. To our knowledge, this is the first report to describe the CLI of αvβ3 (+) tumors in live animals using the daughter products derived from (225)Ac decay in situ. This concept holds promise to further enhance development of targeted alpha particle therapy.

  20. Preliminary Therapy Evaluation of 225Ac-DOTA-c(RGDyK) Demonstrates that Cerenkov Radiation Derived from 225Ac Daughter Decay Can Be Detected by Optical Imaging for In Vivo Tumor Visualization

    Science.gov (United States)

    Pandya, Darpan N.; Hantgan, Roy; Budzevich, Mikalai M.; Kock, Nancy D.; Morse, David L.; Batista, Izadora; Mintz, Akiva; Li, King C.; Wadas, Thaddeus J.

    2016-01-01

    The theranostic potential of 225Ac-based radiopharmaceuticals continues to increase as researchers seek innovative ways to harness the nuclear decay of this radioisotope for therapeutic and imaging applications. This communication describes the evaluation of 225Ac-DOTA-c(RGDyK) in both biodistribution and Cerenkov luminescence imaging (CLI) studies. Initially, La-DOTA-c(RGDyK) was prepared as a non-radioactive surrogate to evaluate methodologies that would contribute to an optimized radiochemical synthetic strategy and estimate the radioactive conjugate's affinity for αvβ3, using surface plasmon resonance spectroscopy. Surface plasmon resonance spectroscopy studies revealed the IC50 and Ki of La-DOTA-c(RGDyK) to be 33 ± 13 nM and 26 ± 11 nM, respectively, and suggest that the complexation of the La3+ ion to the conjugate did not significantly alter integrin binding. Furthermore, use of this surrogate allowed optimization of radiochemical synthesis strategies to prepare 225Ac-DOTA-c(RGDyK) with high radiochemical purity and specific activity similar to other 225Ac-based radiopharmaceuticals. This radiopharmaceutical was highly stable in vitro. In vivo biodistribution studies confirmed the radiotracer's ability to target αvβ3 integrin with specificity; specificity was detected in tumor-bearing animals using Cerenkov luminescence imaging. Furthermore, tumor growth control was achieved using non-toxic doses of the radiopharmaceutical in U87mg tumor-bearing nude mice. To our knowledge, this is the first report to describe the CLI of αvβ3+ tumors in live animals using the daughter products derived from 225Ac decay in situ. This concept holds promise to further enhance development of targeted alpha particle therapy. PMID:27022417

  1. Positron emission tomography study on pancreatic somatostatin receptors in normal and diabetic rats with {sup 68}Ga-DOTA-octreotide: A potential PET tracer for beta cell mass measurement

    Energy Technology Data Exchange (ETDEWEB)

    Sako, Takeo [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Division of Molecular Imaging, Institute of Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Hasegawa, Koki; Nishimura, Mie; Kanayama, Yousuke; Wada, Yasuhiro; Hayashinaka, Emi; Cui, Yilong; Kataoka, Yosky [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Senda, Michio [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Division of Molecular Imaging, Institute of Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Watanabe, Yasuyoshi, E-mail: yywata@riken.jp [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan)

    2013-12-06

    Highlights: •PET images showed high uptake of {sup 68}Ga-DOTA-octreotide in the normal pancreas. •{sup 68}Ga-DOTA-octreotide specifically binds to somatostatin receptors in the pancreas. •The pancreatic uptake of {sup 68}Ga-DOTA-octreotide was decreased in the diabetic rats. •{sup 68}Ga-DOTA-octreotide could be a candidate PET probe to measure the beta cell mass. -- Abstract: Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, and the loss or dysfunction of pancreatic beta cells has been reported before the appearance of clinical symptoms and hyperglycemia. To evaluate beta cell mass (BCM) for improving the detection and treatment of DM at earlier stages, we focused on somatostatin receptors that are highly expressed in the pancreatic beta cells, and developed a positron emission tomography (PET) probe derived from octreotide, a metabolically stable somatostatin analog. Octreotide was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a chelating agent, and labeled with {sup 68}Gallium ({sup 68}Ga). After intravenous injection of {sup 68}Ga-DOTA-octreotide, a 90-min emission scan of the abdomen was performed in normal and DM model rats. The PET studies showed that {sup 68}Ga-DOTA-octreotide radioactivity was highly accumulated in the pancreas of normal rats and that the pancreatic accumulation was significantly reduced in the rats administered with an excess amount of unlabeled octreotide or after treatment with streptozotocin, which was used for the chemical induction of DM in rats. These results were in good agreement with the ex vivo biodistribution data. These results indicated that the pancreatic accumulation of {sup 68}Ga-DOTA-octreotide represented specific binding to the somatostatin receptors and reflected BCM. Therefore, PET imaging with {sup 68}Ga-DOTA-octreotide could be a potential tool for evaluating BCM.

  2. Comparative study on DOTA-derivatized bombesin analog labeled with 90Y and 177Lu: in vitro and in vivo evaluation

    International Nuclear Information System (INIS)

    Introduction: The aim of the study was to compare in vitro and in vivo a novel DOTA-chelated bombesin (BN) analog of the amino acid sequence, QRLGNQWAVGHLM-CONH2 (BN[2-14]NH2), labeled with 90Y and 177Lu, for its potential use in targeted radiotherapy of tumors expressing gastrin releasing peptide (GRP) receptors. The same amino acid sequence, but with different chelator, referred as BN1.1 (Gly-Gly-Cys-Aca-QRLGNQWAVGHLM-CONH2), has already been studied and reported; however, the DOTA-chelated one, suitable for labeling with M+3 type radiometals, was not yet described. Methods: The conditions for labeling of DOTA-BN[2-14]NH2 with noncarrier added 90Y and with 177Lu [specific activity (SA), 15 Ci/mg Lu] were investigated and optimized to provide 90Y-DOTA-BN[2-14]NH2 and 177Lu-DOTA-BN[2-14]NH2 of high SA. The stability of the radiolabeled compounds in human serum was evaluated over a period of 24 h. The human prostate cancer cell line PC-3, known to express GRP receptors, was used for in vitro evaluation of radiolabeled peptide affinity to GRP receptors and for assessment of cytotoxicity of both nonlabeled and radiolabeled peptide. Biodistribution accompanied by receptor blocking was studied in normal Swiss mice. Results: 90Y-DOTA-BN[2-14]NH2 and 177Lu-DOTA-BN[2-14]NH2 were obtained with radiochemical yield >98% and high SA (67.3 GBq 90Y/μmol and 33.6 GBq 177Lu/μmol, respectively). They were stable when incubated in human serum for up to 24 h. The binding affinities of DOTA-BN[2-14]NH2 and both natY- and natLu-labeled analogs to GRP receptors were high (IC50=1.78, 1.99, and 1.34 nM, respectively), especially for the natLu-DOTA-BN[2-14]NH2 complex. The cytotoxicity study of DOTA-BN[2-14]NH2 to PC-3 cells revealed an IC50=6300 nM after 72 h of exposition, while the labeled derivatives showed no significant cytotoxic effect. The internalization rate to PC-3 cells was more rapid for 177Lu-labeled peptide (84.87%) than for the 90Y-labeled one (80.79%), while the efflux

  3. Molecular Evolution of the dotA Gene in Legionella pneumophila

    OpenAIRE

    Ko, Kwan Soo; Hong, Seong Karp; Lee, Hae Kyung; Park, Mi-Yeoun; Kook, Yoon-Hoh

    2003-01-01

    The molecular evolution of dotA, which is related to the virulence of Legionella pneumophila, was investigated by comparing the sequences of 15 reference strains (serogroups 1 to 15). It was found that dotA has a complex mosaic structure. The whole dotA gene of Legionella pneumophila subsp. pneumophila serogroups 2, 6, and 12 has been transferred from Legionella pneumophila subsp. fraseri. A discrepancy was found between the trees inferred from the nucleotide and deduced amino acid sequences ...

  4. Identification, characterization and suppression of side-products formed during the synthesis of high dose 68Ga-DOTA-TATE

    International Nuclear Information System (INIS)

    In the course of the establishment of 68Ga-DOTA-TATE production for clinical use a shoulder comprising presumably several impurities was observed in the chromatogram of the analytical radio-HPLC. LC–MS/MS results support the hypothesis that some of these radioimpurities are radiolytic oxidation by-products of 68Ga-DOTA-TATE. A new HPLC method was developed for quality control of 68Ga-DOTA-TATE. Significant improvement on the radiochemical purity of 68Ga-DOTA-TATE was achieved by the addition of ascorbic acid or ethanol to the reaction mixture. - Highlights: ► A new HPLC method was developed for quality control of 68Ga-DOTA-TATE. ► Radiolytic oxidation by-products of 68Ga-DOTA-TATE were formed at high dose of activity. ► It is necessary to add ascorbic acid or ethanol to the preparation for high dose of 68Ga-DOTA-TATE

  5. Y-90-DOTA-hLL2: An Agent for Radioimmunotherapy of Non-Hodgkin's Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Griffiths, Gary L.(Immunomedics, Inc.); Govindan, Serengulam V.(Immunomedics, Inc.); Sharkey, Robert M.(Immunomedics, Inc.); Fisher, Darrell R.(BATTELLE (PACIFIC NW LAB)); Goldenberg, David M.(Immunomedics, Inc.)

    2003-01-01

    The goal of this work was to determine an optimal radioimmunotherapy agent for non-Hodgkin's lymphoma. We established the stability profile of yttrium-90-labeled humanized LL2 (hLL2) monoclonal antibody prepared with different chelating agents, and from these data estimated the improvement using the most stable yttrium-90 chelate-hLL2 complex. Methods: The complementary-determining region- (cdr)-grafted (humanized) anti-CD22 mAb, hLL2 (epratuzumab), was conjugated to derivatives of DTPA and 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA). The conjugates were labeled with Y-90 and tested against a 10,000-fold molar excess of free DTPA and against human serum. The conjugates were also labeled with Y-88 and compared for biodistribution in normal and lymphoma xenograft-bearing athymic mice. In vivo data were analyzed for uptake of yttrium in bone and washed bone when either the DOTA or the Mx-DTPA chelates were used, and dosimetry calculations were made for each. Results: Y-90-DOTA -mAb were stable to either DTPA or serum challenge. DTPA complexes of hLL2 lost 3-4% of Y-90 (days 1-4) and 10-15% thereafter. In vivo, stability differences showed lower Y-90 uptake in bone using DOTA. Absorbed doses per 37 MBq (1 mCi) Y-90-mAb were 3555 and 5405 cGy for bone, and 2664 and 4524 cGy for washed-bone for 90Y-DOTA-hLL2 and 90Y-MxDTPA-hLL2, respectively, amounting to 52% and 69.8% increases in absorbed radiation doses for bone and washed-bone when switching from a DOTA to a Mx-DTPA chelate. Conclusion: Y-90-hLL2 prepared with the DOTA chelate represents a preferred agent for RAIT of non-Hodgkin's lymphoma, with an in vivo model demonstrating a large reduction in bone-deposited yttrium, as compared to yttrium-90-hLL2 agents prepared with open-chain DTPA-type chelating agents. Dosimetry suggests that this will result in a substantial toxicological advantage for a DOTA-based hLL2 conjugate.

  6. TmDOTA -: A Sensitive Probe for MR Thermometry in Vivo

    Science.gov (United States)

    Zuo, Chun S.; Mahmood, Ashfaq; Sherry, A. Dean

    2001-07-01

    The lanthanide complex, thulium 1,4,7,10-tetraazacyclodo- decane-1,4,7,10-tetraacetic acid (TmDOTA-), has been investigated as an agent for MR thermometry in vivo. The chemical shifts of the TmDOTA- protons were highly sensitive to temperature at a clinically relevant field strength, yet insensitive to pH and the presence of Ca2+. Given the excellent stability of lanthanide-DOTA complexes and high thermal sensitivity, TmDOTA- is expected to be a good candidate for MR thermometry in vivo.

  7. Reducing Renal Uptake of 177Lu Labeled CCK Derivative using Basic Amino Acids

    International Nuclear Information System (INIS)

    Radiolabeled peptides have been designed to target the relative receptors overespressed in tumor cells, such as integrin αvβ3, gastrin-releasing peptide receptor (GRPR), melanocortin-1 receptor (MC1-R), glucagon-like peptide-a receptor (GLP-1R), and cholecystokinin (CCK) receptor. Most of these peptides are eliminated from the body via the kidney and are partly reabsorbed in the proximal tubular cells. However, the high renal uptake of the radiolabeled peptides may lead to renal toxicity. In this study we investigated various amino acid solutions to reduce the renal uptake of 177Lu-DOTA-CCK derivative. Renal uptake of 177Lu-DOTA-CCK derivative is effectively reduced by the administration of positively charged amino acids. The administration of 12 mg of L-lysine was as effective in reducing the renal uptake as 6 mg of lysine and 6 mg of arginine combinations. Further studies will be performed to identify the most potent inhibitor of renal reuptake of radiolabeled peptides and minimize the chance of unwanted side effects

  8. Reducing Renal Uptake of {sup 177}Lu Labeled CCK Derivative using Basic Amino Acids

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Soyoung; Lim, Jaecheong; Joh, Eunha [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    Radiolabeled peptides have been designed to target the relative receptors overespressed in tumor cells, such as integrin αvβ3, gastrin-releasing peptide receptor (GRPR), melanocortin-1 receptor (MC1-R), glucagon-like peptide-a receptor (GLP-1R), and cholecystokinin (CCK) receptor. Most of these peptides are eliminated from the body via the kidney and are partly reabsorbed in the proximal tubular cells. However, the high renal uptake of the radiolabeled peptides may lead to renal toxicity. In this study we investigated various amino acid solutions to reduce the renal uptake of {sup 177}Lu-DOTA-CCK derivative. Renal uptake of {sup 177}Lu-DOTA-CCK derivative is effectively reduced by the administration of positively charged amino acids. The administration of 12 mg of L-lysine was as effective in reducing the renal uptake as 6 mg of lysine and 6 mg of arginine combinations. Further studies will be performed to identify the most potent inhibitor of renal reuptake of radiolabeled peptides and minimize the chance of unwanted side effects.

  9. Preparation of DOTA-TATE and DOTA-NOC freeze-dried kits for formulation of patient doses of 177Lu-labeled agents and their comparison for peptide receptor radionuclide therapy application

    International Nuclear Information System (INIS)

    The objective of the present work is to prepare freeze-dried DOTA-TATE and DOTA-NOC kits for the easy and convenient preparation of patient doses of 177Lu-DOTA-TATE and 177Lu-DOTA-NOC, respectively at the hospital radiopharmacy and to compare the radio-peptides with respect to their radiochemical and biological behaviors. Freeze-dried kits of DOTA-TATE and DOTA-NOC, comprising a lyophilized mixture of 200 μg of DOTA-peptide, 80 mg of gentisic acid and 13.9 mg of ammonium acetate were prepared. Therapeutic doses of 177Lu-labeled peptides (up to 200 mCi, 7.4 GBq) were prepared using these kits and 177Lu, produced in-house, with >99 % radiochemical purity and high stability following an easy and convenient protocol. Comparative pharmacokinetic behavior of the radio-peptides was studied by carrying out biodistribution studies in normal Wistar rats which revealed higher retention of activity in several major organs and slower renal clearance for 177Lu-DOTA-NOC compared to that of 177Lu-DOTA-TATE. Preliminary pharmacokinetic studies, carried out in limited number of patients suffering from cancers of neuroendocrine origins, showed lower accumulation of activity in vital organs and faster renal clearance of 177Lu-DOTA-TATE compared to that of 177Lu-DOTA-NOC. (author)

  10. Development of [90Y]DOTA-conjugated bisphosphonate for treatment of painful bone metastases

    International Nuclear Information System (INIS)

    Introduction: Based on the concept of bifunctional radiopharmaceuticals, we have previously developed 186Re-complex-conjugated bisphosphonate analogs for palliation of painful bone metastases and have demonstrated the utility of these compounds. By applying a similar concept, we hypothesized that a bone-specific directed 90Y-labeled radiopharmaceutical could be developed. Methods: In this study, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was chosen as the chelating site, and DOTA was conjugated with 4-amino-1-hydroxybutylidene-1,1-bisphosphonate. [90Y]DOTA-complex-conjugated bisphosphonate ([90Y]DOTA-HBP) was prepared by coordination with 90Y, and its biodistribution was studied in comparison to [90Y]citrate. Results: In biodistribution experiments, [90Y]DOTA-HBP and [90Y]citrate rapidly accumulated and resided in the bone. Although [90Y]citrate showed a higher level of accumulation in the bone than [90Y]DOTA-HBP, the clearances of [90Y]DOTA-HBP from the blood and from almost all soft tissues were much faster than those of [90Y]citrate. As a result, the estimated absorbed dose ratios of soft tissues to osteogenic cells (target organ) of [90Y]DOTA-HBP were lower than those of [90Y]citrate. Conclusions: [90Y]DOTA-HBP showed superior biodistribution characteristics as a bone-seeking agent and led to a decrease in the level of unnecessary radiation compared to [90Y]citrate. Since the DOTA ligand forms a stable complex not only with 90Y but also with lutetium (177Lu), indium (111In), gallium (67/68Ga), gadolinium (Gd) and so on, complexes of DOTA-conjugated bisphosphonate with various metals could be useful as agents for palliation of metastatic bone pain, bone scintigraphy and magnetic resonance imaging

  11. Drug Nanoparticle Formulation Using Ascorbic Acid Derivatives

    OpenAIRE

    Kunikazu Moribe; Waree Limwikrant; Kenjirou Higashi; Keiji Yamamoto

    2011-01-01

    Drug nanoparticle formulation using ascorbic acid derivatives and its therapeutic uses have recently been introduced. Hydrophilic ascorbic acid derivatives such as ascorbyl glycoside have been used not only as antioxidants but also as food and pharmaceutical excipients. In addition to drug solubilization, drug nanoparticle formation was observed using ascorbyl glycoside. Hydrophobic ascorbic acid derivatives such as ascorbyl mono- and di-n-alkyl fatty acid derivatives are used either as drugs...

  12. PEGylated DOTA-AHA-based Gd(III) chelates – A relaxometric study

    OpenAIRE

    Fontes, André; Karimib, Shima; Helm, Lothar; Ferreira, Paula M.T.; André, João P.

    2015-01-01

    Three PEGylated derivatives of 1,4,7,10-tetraazacyclododecane-1-((6-amino)hexanoic)-4,7,10-triacetic acid) (DOTA-AHA) with different molecular weights were prepared and characterized. Their Gd(III) chelates were studied in aqueous solution using variable-temperature 1H nuclear magnetic relaxation dispersion (NMRD) and 17ONMR spectroscopy in view of the determination of their relaxivity and the parameters that govern it. The relaxivity varied from 5.1 to 6.5 mM-1.s-1 (37 ºC and 60 MHz) with t...

  13. DOTA-Functionalized Polylysine: A High Number of DOTA Chelates Positively Influences the Biodistribution of Enzymatic Conjugated Anti-Tumor Antibody chCE7agl

    OpenAIRE

    Jürgen Grünberg; Simone Jeger; Dikran Sarko; Patrick Dennler; Kurt Zimmermann; Walter Mier; Roger Schibli

    2013-01-01

    Site-specific enzymatic reactions with microbial transglutaminase (mTGase) lead to a homogenous species of immunoconjugates with a defined ligand/antibody ratio. In the present study, we have investigated the influence of different numbers of 1,4,7,10-tetraazacyclododecane-N-N'-N''-N'''-tetraacetic acid (DOTA) chelats coupled to a decalysine backbone on the in vivo behavior of the chimeric monoclonal anti-L1CAM antibody chCE7agl. The enzymatic conjugation of (DOTA)1-decalysine, (DOTA)3-decaly...

  14. In vivo evaluation of a radiogallium-labeled bifunctional radiopharmaceutical, Ga-DOTA-MN2, for hypoxic tumor imaging

    International Nuclear Information System (INIS)

    On the basis of the findings obtained by X-ray crystallography of gadolinium-diethylenetriamine pentaacetic acid (Ga-DOTA) chelates and the drug design concept of bifunctional radiopharmaceuticals, we previously designed and synthesized a radiogallium-labeled DOTA chelate containing two metronidazole moieties, 67Ga-DOTA-MN2, for hypoxic tumor imaging. As expected, 67Ga-DOTA-MN2 exhibited high in vivo stability, although two carboxyl groups in the DOTA skeleton were conjugated with metronidazole moieties. In this study, we evaluated 67/68Ga-DOTA-MN2 as a nuclear imaging agent for hypoxic tumors. 67Ga-labeling of DOTA-MN2 with 67GaCl3 was achieved with high radiochemical yield (>85%) by 1-min of microwave irradiation (50 W). The pharmacokinetics of 67Ga-DOTA-MN2 were examined in mammary carcinoma (FM3A) tumor-bearing mice, and compared with those of 67Ga-DOTA-MN1 containing one metronidazole unit and '67Ga-DOTA. Upon administration, 67Ga-DOTA-MN2 exhibited higher accumulation in the implanted tumors than '67Ga-DOTA. Tumor-to-blood ratios of 67Ga-DOTA-MN2 were about two-fold higher than those of 67Ga-DOTA-MN1. Autoradiographic analysis showed the heterogeneous localization of '67Ga-DOTA-MN2 in the tumors, which corresponds to hypoxic regions suggested by well-established hypoxia marker drug, pimonidazole. Furthermore, in positron emission tomography (PET) study, the tumors of mice administered '68Ga-labeled DOTA-MN2 were clearly imaged by small-animal PET at 1 h after administration. This study demonstrates the potential usefulness of 67/68Ga-DOTA-MN2 as a nuclear imaging agent for hypoxic tumors and suggests that two functional moieties, such as metronidazole, can be conjugated to radiogallium-DOTA chelate without reducing the complex stability. The present findings provide useful information about the chemical design of radiogallium-labeled radiopharmaceuticals for PET and single photon emission computed tomography (SPECT) studies. (author)

  15. Drug Nanoparticle Formulation Using Ascorbic Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Kunikazu Moribe

    2011-01-01

    Full Text Available Drug nanoparticle formulation using ascorbic acid derivatives and its therapeutic uses have recently been introduced. Hydrophilic ascorbic acid derivatives such as ascorbyl glycoside have been used not only as antioxidants but also as food and pharmaceutical excipients. In addition to drug solubilization, drug nanoparticle formation was observed using ascorbyl glycoside. Hydrophobic ascorbic acid derivatives such as ascorbyl mono- and di-n-alkyl fatty acid derivatives are used either as drugs or carrier components. Ascorbyl n-alkyl fatty acid derivatives have been formulated as antioxidants or anticancer drugs for nanoparticle formulations such as micelles, microemulsions, and liposomes. ASC-P vesicles called aspasomes are submicron-sized particles that can encapsulate hydrophilic drugs. Several transdermal and injectable formulations of ascorbyl n-alkyl fatty acid derivatives were used, including ascorbyl palmitate.

  16. Biological activities of substituted trichostatic acid derivatives

    Indian Academy of Sciences (India)

    Cédric Charrier; Joëlle Roche; Jean-Pierre Gesson; Philippe Bertrand

    2009-07-01

    New substituted trichostatic acid derivatives have been synthesized and evaluated for their biological activities towards the H661 non-small lung cancer cell line. These syntheses were achieved by alkylation of propiophenones to introduce the side chain with a terminal precursor of hydroxamic acid and aminobenzamide derivatives. The first fluorinated derivatives of trichostatic acid are described, such as 6-fluoro trichostatin A, with antiproliferative activities in the micromolar range and with histone deacetylase inhibitory activity.

  17. Stereoselective Synthesis of 1-Aminocyclopropanecarboxylic Acid Derivatives via Ylide Cyclopropanation of Dehydroamino Acid Derivatives

    Institute of Scientific and Technical Information of China (English)

    Zhou Rui; Deng Xianming; Zheng Juncheng; Shen Qi; Sun Xiuli; Tang Yong

    2011-01-01

    1-Aminocyclopropanecarboxylic acid derivatives are synthesized from readily available dehydroamino acid de-rivatives via sulfur ylide. A range of different ylides are employed and the corresponding aminocyclopropanes are afforded with reasonable diastereoselection in good yields.

  18. Complexes of salicylic acid and its derivatives

    International Nuclear Information System (INIS)

    A generalization and systematization have been made of literature data on complexing of various elements, including beryllium, cadmium, boron, indium, rare-earth elements, actinides, and transition elements with salicylic acid and it derivatives (amino-, nitro- and halosalicylic acids). The effect of the position and nature of the substitute, in the case of salicylic acid derivatives, on the complexing process is discussed. Certain physicochemical properties of the complexes under consideration are described along with data indicative of their stability

  19. Gallium-68-DOTA-albumin as a PET blood-pool marker: experimental evaluation in vivo

    International Nuclear Information System (INIS)

    Investigations into tumor angiogenesis and antiangiogenic treatment have renewed interest in tumor perfusion. To image tumor blood-pool by PET, suitable tracers are not generally available. In this experimental study, we characterized a 68Ga-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) conjugate of rat serum albumin (68Ga-DOTA-RSA) in vivo using a generator-produced isotope. Biodistribution was determined in ACI rats after intravenous administration of 3-6 MBq of 68Ga-DOTA-RSA. Three ACI rats were imaged over 1 h by dynamic PET after intravenous administration of 15-25 MBq of 68Ga-DOTA-RSA while the blood-pool activity was recorded simultaneously in a closed extracorporeal loop (ECL) between the carotid artery and the jugular vein. Time-activity curves (TACs) were obtained from volume of interest (VOI) analysis and from the ECL data. Stability and metabolites in plasma and urine were analyzed by size exclusion HPLC (SE-HPLC) 1 h after intravenous injection of 67Ga-DOTA-RSA. Blood radioactivity decreased by 10% and 18% from 10 to 60 min p.i. by biodistribution and PET or ECL, respectively. Tissue sampling between 10 and 60 min p.i. showed slight increases in the uptake of spleen, myocardium, kidney and skeletal muscle while hepatic accretion remained unchanged. Total urinary excretion after 60 min amounted to 9% of the injected dose. HPLC demonstrated a single urinary metabolite corresponding in size to gallium-labeled DOTA. 68Ga-DOTA-RSA is a blood-pool tracer whose physical and biological half-life is well suited for PET. Our findings support clinical imaging using 68Ga-DOTA-labeled human serum albumin (HSA). The generator-produced label makes 68Ga-DOTA-labeled albumin continuously available even to centers lacking an in-house cyclotron

  20. DOTA alpha-melanocyte-stimulating hormone analogues for imaging metastatic melanoma lesions.

    Science.gov (United States)

    Froidevaux, Sylvie; Calame-Christe, Martine; Sumanovski, Lazar; Tanner, Heidi; Eberle, Alex N

    2003-06-01

    Scintigraphic imaging of metastatic melanoma lesions requires highly tumor-specific radiopharmaceuticals. Because both melanotic and amelanotic melanomas overexpress melanocortin-1 receptors (MC1R), radiolabeled analogues of alpha-melanocyte-stimulating hormone (alpha-MSH) are potential candidates for melanoma diagnosis. Here, we report the in vivo performance of a newly designed octapeptide analogue, [betaAla(3), Nle(4), Asp(5), D-Phe(7), Lys(10)]-alpha-MSH(3-10) (MSH(OCT)), which was conjugated through its N-terminal amino group to the metal chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to enable incorporation of radiometals (e.g., indium-111) into the peptide. DOTA-MSH(OCT) displayed high in vitro MC1R affinity (IC(50) 9.21 nM). In vivo [(111)In]DOTA-MSH(OCT) exhibited a favorable biodistribution profile after injection in B16-F1 tumorbearing mice. The radiopeptide was rapidly cleared from blood through the kidneys and, most importantly, accumulated preferentially in the melanoma lesions. Lung and liver melanoma metastases could be clearly imaged on tissue section autoradiographs 4 h after injection of [(111)In]DOTA-MSH(OCT). A comparative study of [(111)In]DOTA-MSH(OCT) with [(111)In]DOTA-[Nle(4), D-Phe(7)]-alpha-MSH ([(111)In]-DOTA-NDP-MSH) demonstrated the superiority of the DOTA-MSH(OCT) peptide, particularly for the amount of radioactivity taken up by nonmalignant organs, including bone, the most radiosensitive tissue. These results demonstrate that [(111)In]DOTA-MSH(OCT) is a promising melanoma imaging agent.

  1. Synthesis and in vivo evaluation of {sup 201}Tl(III)-DOTA complexes for applications in SPECT imaging

    Energy Technology Data Exchange (ETDEWEB)

    Hijnen, Nicole M.; Vries, Anke de [Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven (Netherlands); Blange, Roy [Department of Biomolecular Engineering, Antwerp University, 2610 Antwerp (Belgium); Burdinski, Dirk [Department of Biomolecular Engineering, Philips Research, 5656 AE Eindhoven (Netherlands); Gruell, Holger, E-mail: h.gruell@tue.n [Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven (Netherlands); Department of Biomolecular Engineering, Philips Research, 5656 AE Eindhoven (Netherlands)

    2011-05-15

    Introduction: The aim of this study was to assess the use of {sup 201}thallium{sup 3+} ({sup 201}Tl{sup 3+}) as a radiolabel for nuclear imaging tracers. Methods for labeling of 1,4,7,10-tetraazacyclododecane-N,N',N'',N''' tetraacetic acid (DOTA) and diethylenetriaminepentaacetic acid (DTPA) chelators with {sup 201}Tl{sup 3+} were investigated, and the levels of stability of these chelates were tested in vitro and in vivo. Methods: {sup 201}Tl(I)Cl was treated with hydrochloric acid and ozone to form {sup 201}Tl(III)Cl{sub 3}. The procedure for labeling of DOTA and DTPA was optimized, testing different buffer solutions and pH values. The stability levels of {sup 201}Tl(III)-DOTA and {sup 201}Tl(III)-DTPA were assessed in buffer, mouse serum and human serum (1:1, v/v) at a temperature of 310 K for 48 h. Subsequently, in vivo stability studies with {sup 201}Tl(III)-DOTA were performed, comparing the biodistribution of {sup 201}Tl(III)-DOTA with that of {sup 201}Tl(I)Cl in a single-isotope study and with that of {sup 177}Lu(III)-DOTA in a dual-isotope single photon emission computed tomography study. Results: {sup 201}Tl(III)-DTPA, {sup 201}Tl(III)-DOTA and {sup 177}Lu(III)-DOTA were prepared with >95% radiochemical purity. While {sup 201}Tl(III)-DOTA showed a prolonged level of stability in buffer and serum, {sup 201}Tl was quickly released from DTPA in serum. Apart from some urinary excretion, the biodistribution of DOTA-chelated {sup 201}Tl{sup 3+} was similar to that of free (ionic) {sup 201}Tl{sup +} and did not match the biodistribution of {sup 177}Lu(III)-DOTA. This indicated a limited stability of {sup 201}Tl(III)-DOTA complexes in vivo. Conclusion: Despite promising results on the labeling and in vitro stability of {sup 201}Tl(III)-DOTA, our in vivo results indicate that the integrity of {sup 201}Tl(III)-DOTA decreases to <20% during the time required for urinary excretion, thereby limiting the use of {sup 201}Tl{sup 3+} as a

  2. Synthesis and in vivo evaluation of 201Tl(III)-DOTA complexes for applications in SPECT imaging

    International Nuclear Information System (INIS)

    Introduction: The aim of this study was to assess the use of 201thallium3+ (201Tl3+) as a radiolabel for nuclear imaging tracers. Methods for labeling of 1,4,7,10-tetraazacyclododecane-N,N',N'',N''' tetraacetic acid (DOTA) and diethylenetriaminepentaacetic acid (DTPA) chelators with 201Tl3+ were investigated, and the levels of stability of these chelates were tested in vitro and in vivo. Methods: 201Tl(I)Cl was treated with hydrochloric acid and ozone to form 201Tl(III)Cl3. The procedure for labeling of DOTA and DTPA was optimized, testing different buffer solutions and pH values. The stability levels of 201Tl(III)-DOTA and 201Tl(III)-DTPA were assessed in buffer, mouse serum and human serum (1:1, v/v) at a temperature of 310 K for 48 h. Subsequently, in vivo stability studies with 201Tl(III)-DOTA were performed, comparing the biodistribution of 201Tl(III)-DOTA with that of 201Tl(I)Cl in a single-isotope study and with that of 177Lu(III)-DOTA in a dual-isotope single photon emission computed tomography study. Results: 201Tl(III)-DTPA, 201Tl(III)-DOTA and 177Lu(III)-DOTA were prepared with >95% radiochemical purity. While 201Tl(III)-DOTA showed a prolonged level of stability in buffer and serum, 201Tl was quickly released from DTPA in serum. Apart from some urinary excretion, the biodistribution of DOTA-chelated 201Tl3+ was similar to that of free (ionic) 201Tl+ and did not match the biodistribution of 177Lu(III)-DOTA. This indicated a limited stability of 201Tl(III)-DOTA complexes in vivo. Conclusion: Despite promising results on the labeling and in vitro stability of 201Tl(III)-DOTA, our in vivo results indicate that the integrity of 201Tl(III)-DOTA decreases to 201Tl3+ as a radiolabel for tracer imaging.

  3. Towards the Rational Design of MRI Contrast Agents: δ-Substitution of Lanthanide(III) NB-DOTA-Tetraamide Chelates Influences but Does Not Control Coordination Geometry**

    OpenAIRE

    Carney, Christiane E.; Tran, Anh D.; Jing WANG; Schabel, Matthias C.; Sherry, A. Dean; Woods, Mark

    2011-01-01

    LnDOTA-tetraamide chelates (DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) have received considerable recent attention as a result of their potential to act as PARACEST contrast agents for magnetic resonance imaging (MRI). Although PARACEST agents afford several advantages over conventional contrast agents they suffer from substantially higher detection limits; thus, improving the effectiveness of LnDOTA-tetraamide chelates is an important goal. In this study we investigate th...

  4. Optimization of time-resolved fluorescence assay for detection of europium-tetraazacyclododecyltetraacetic acid-labeled ligand-receptor interactions.

    Science.gov (United States)

    De Silva, Channa R; Vagner, Josef; Lynch, Ronald; Gillies, Robert J; Hruby, Victor J

    2010-03-01

    Lanthanide-based luminescent ligand binding assays are superior to traditional radiolabel assays due to improving sensitivity and affordability in high-throughput screening while eliminating the use of radioactivity. Despite significant progress using lanthanide(III)-coordinated chelators such as diethylenetriaminepentaacetic acid (DTPA) derivatives, dissociation-enhanced lanthanide fluoroimmunoassays (DELFIAs) have not yet been successfully used with more stable chelators (e.g., tetraazacyclododecyltetraacetic acid [DOTA] derivatives) due to the incomplete release of lanthanide(III) ions from the complex. Here a modified and optimized DELFIA procedure incorporating an acid treatment protocol is introduced for use with Eu(III)-DOTA-labeled peptides. Complete release of Eu(III) ions from DOTA-labeled ligands was observed using hydrochloric acid (2.0M) prior to the luminescent enhancement step. [Nle(4),d-Phe(7)]-alpha-melanocyte-stimulating hormone (NDP-alpha-MSH) labeled with Eu(III)-DOTA was synthesized, and the binding affinity to cells overexpressing the human melanocortin-4 (hMC4) receptor was evaluated using the modified protocol. Binding data indicate that the Eu(III)-DOTA-linked peptide bound to these cells with an affinity similar to its DTPA analogue. The modified DELFIA procedure was further used to monitor the binding of an Eu(III)-DOTA-labeled heterobivalent peptide to the cells expressing both hMC4 and cholecystokinin-2 (CCK-2) receptors. The modified assay provides superior results and is appropriate for high-throughput screening of ligand libraries. PMID:19852924

  5. Cholic acid derivatives: novel antimicrobials.

    Science.gov (United States)

    Savage, P B; Li, C

    2000-02-01

    Mimics of squalamine and polymyxin B (PMB) have been prepared from cholic acid in hope of finding new antimicrobial agents. The squalamine mimics include the polyamine and sulphate functionalities found in the parent antibiotic, however, the positions relative to the steroid nucleus have been exchanged. The PMB mimics include the conservation of functionality among the polymyxin family of antibiotics, the primary amine groups and a hydrophobic chain. Although the squalamine and PMB mimics are morphologically dissimilar, they display similar activities. Both are simple to prepare and demonstrate broad spectrum antimicrobial activity against Gram-negative and Gram-positive organisms. Specific examples may be inactive alone, yet effectively permeabilise the outer membranes of Gram-negative bacteria rendering them sensitive to hydrophobic antibiotics. Problems associated with some of the squalamine and PMB mimics stem from their haemolytic activity and interactions with serum proteins, however, examples exist without these side effects which can sensitise Gram-negative bacteria to hydrophobic antibiotics. PMID:11060676

  6. Value of 111In-DOTA-lanreotide and 111In-DOTA-DPhe1-Tyr3-octreotide in differentiated thyroid cancer: results of in vitro binding studies and in vivo comparison with 18F-FDG PET

    International Nuclear Information System (INIS)

    Radioiodine-negative thyroid cancer presents diagnostic and therapeutic difficulties, warranting the implementation of new imaging and treatment strategies. The purpose of this study was twofold. First, we investigated in vitro the binding characteristics of 111In-DOTA-lanreotide (111In-DOTA-LAN) and 111In-DOTA-DPhe1-Tyr3-octreotide (111In-DOTA-TOC) to cells derived from differentiated thyroid cancer (DTC). Second, we evaluated the value of somatostatin receptor (SSTR) scintigraphy with these radioligands, as compared with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), for the detection of tumour lesions in DTC patients. Binding of 111In-DOTA-LAN and 111In-DOTA-TOC to cells isolated from surgically removed thyroid tissue was evaluated in vitro by performing saturation and displacement studies. Eighteen DTC patients with elevated thyroglobulin (12 radioiodine-negative, six radioiodine-positive) were investigated with 111In-DOTA-LAN, 111In-DOTA-TOC and 18F-FDG PET scans. Large numbers of SSTR binding sites for 111In-DOTA-LAN and 111In-DOTA-TOC were found on the cells investigated. Both SSTR radioligands exhibited a high binding affinity for these SSTR binding sites. 111In-DOTA-LAN and 111In-DOTA-TOC scintigraphy detected 37 and 33 lesions, respectively, in 17 (94%) patients each, whereas 18F-FDG PET revealed 30 lesions in 15 (83%) patients. Uptake of both SSTR radioligands was found in several radioiodine-negative sites. No striking differences in lesion imaging by 111In-DOTA-LAN and 111In-DOTA-TOC were found. In both radioiodine-negative and radioiodine-positive patients, more lesions were SSTR-positive/18F-FDG-negative than were 18F-FDG-positive/SSTR-negative. Adding a SSTR scan with these radioligands to the diagnostic work-up increases the diagnostic capacity in DTC, and should be considered particularly in radioiodine-negative patients with elevated thyroglobulin levels. (orig.)

  7. Identification, characterization and suppression of side-products formed during the synthesis of high dose ⁶⁸Ga-DOTA-TATE.

    Science.gov (United States)

    Mu, Linjing; Hesselmann, Rolf; Oezdemir, Ufuk; Bertschi, Louis; Blanc, Alain; Dragic, Martina; Löffler, Dirk; Smuda, Christoph; Johayem, Anass; Schibli, Roger

    2013-06-01

    In the course of the establishment of (68)Ga-DOTA-TATE production for clinical use a shoulder comprising presumably several impurities was observed in the chromatogram of the analytical radio-HPLC. LC-MS/MS results support the hypothesis that some of these radioimpurities are radiolytic oxidation by-products of (68)Ga-DOTA-TATE. A new HPLC method was developed for quality control of (68)Ga-DOTA-TATE. Significant improvement on the radiochemical purity of (68)Ga-DOTA-TATE was achieved by the addition of ascorbic acid or ethanol to the reaction mixture.

  8. Identification, characterization and suppression of side-products formed during the synthesis of high dose ⁶⁸Ga-DOTA-TATE.

    Science.gov (United States)

    Mu, Linjing; Hesselmann, Rolf; Oezdemir, Ufuk; Bertschi, Louis; Blanc, Alain; Dragic, Martina; Löffler, Dirk; Smuda, Christoph; Johayem, Anass; Schibli, Roger

    2013-06-01

    In the course of the establishment of (68)Ga-DOTA-TATE production for clinical use a shoulder comprising presumably several impurities was observed in the chromatogram of the analytical radio-HPLC. LC-MS/MS results support the hypothesis that some of these radioimpurities are radiolytic oxidation by-products of (68)Ga-DOTA-TATE. A new HPLC method was developed for quality control of (68)Ga-DOTA-TATE. Significant improvement on the radiochemical purity of (68)Ga-DOTA-TATE was achieved by the addition of ascorbic acid or ethanol to the reaction mixture. PMID:22939572

  9. Synthesis of β-Amino Acid Derivatives

    Institute of Scientific and Technical Information of China (English)

    Zhao Yonghua; Ma Zhihua; Jiang Nan; Wang Jianbo

    2004-01-01

    In recent years, β-amino acids and their derivatives have attracted considerable attention due to their occurrence in biologically active natural products, such as dolastatins,cyclohexylnorstatine and Taxol. β-Amino acids also find application in the synthesis of β-lactams,piperidines, indolizidines. Moreover, the peptides consisting of β-amino acids, the so-called β-peptides, have been extensively studied recently. Consequently, considerable efforts have been directed to the synthesis of β-amino acids and their derivatives1. In particular, stereoselective synthesis of β-amino acids has been a challenging project, and there are only limited methods available. In this presentation, we report our efforts in this area.

  10. Synthesis of isothiocyanate-derived mercapturic acids

    NARCIS (Netherlands)

    Vermeulen, M.; Zwanenburg, B.; Chittenden, G.J.F.; Verhagen, H.

    2003-01-01

    Twelve mercapturic acids derived from saturated and unsaturated aliphatic and aromatic isothiocyanates were synthesised, by adding isothiocyanate to a solution of N-acetyl-L-cysteine and sodium bicarbonate, in a typical yield of 77%. Isothiocyanates were synthesised first by adding the corresponding

  11. Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ji-Ae, E-mail: jpark@kirams.re.kr [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yong Jin; Ko, In Ok [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Tae-Jeong; Chang, Yongmin [Institute of Biomedical Engineering, Kyungpook National University, Daegu (Korea, Republic of); Lim, Sang Moo [Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Kyeong Min [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Jung Young, E-mail: jykim@kirams.re.kr [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2014-12-12

    Highlights: • Development of improved tumor-targeting MRI contrast agents. • To increase the targeting ability of RGD, we developed cycloalkane-based RGD peptides. • Gd(DOTA) conjugates of cycloalkane-based RGD peptide show improved tumor signal enhancement in vivo MR images. - Abstract: Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images.

  12. Comparison of yttrium and indium complexes of DOTA-BA and DOTA-MBA: models for (90)Y- and (111)In-labeled DOTA-biomolecule conjugates.

    Science.gov (United States)

    Liu, Shuang; Pietryka, John; Ellars, Charles E; Edwards, D Scott

    2002-01-01

    Yttrium and indium complexes of 1,4,7,10-tetraaza-4,7,10-tris(carboxymethyl)-1-cyclododecylacetylbenzylamine (DOTA-BA) and 1,4,7,10-tetraaza-4,7,10-tris(carboxymethyl)-1-cyclododecylacetyl-R-(+)-alpha-methylbenzylamine (DOTA-MBA) were prepared in order to study solution structures of (90)Y- and (111)In-labeled DOTA-biomolecule conjugates. (90)Y and (111)In complexes M(L) (M = (90)Y and (111)In; L = DOTA-BA and DOTA-MBA) were prepared from the reaction of MCl(3) with DOTA-BA and DOTA-MBA, respectively, in ammonium acetate buffer. A reverse phase HPLC method revealed that both (90)Y and (111)In complexes show only one radiometric peak in their radio-HPLC chromatograms. It was also found that (111)In(DOTA-BA) and (111)In(DOTA-MBA) are more hydrophilic than their corresponding (90)Y analogues, suggesting different coordination spheres in (111)In and (90)Y complexes of the same DOTA conjugate. Complexes M(L) (M = Y and In; L = DOTA-BA and DOTA-MBA) were prepared and characterized by HPLC, LC-MS, and NMR ((1)H and (13)C) methods. The HPLC concordance experiments for (90)Y(DOTA-MBA)/Y(DOTA-MBA) and (111)In(DOTA-MBA)/In(DOTA-MBA) show that the same complex is prepared at both tracer and macroscopic levels. The NMR data ((1)H and (13)C) clearly demonstrates that Y(DOTA-BA) and Y(DOTA-MBA) exist in solution as one predominant isomer. VT NMR data ((1)H and (13)C) show that In(DOTA-BA) and In(DOTA-MBA) are fluxional at room temperature while Y(DOTA-BA) and Y(DOTA-MBA) become fluxional only at elevated temperatures. The fluxionality of these complexes is due to rapid rotation of acetate/acetamide chelating arms and inversion of ethylenic groups of the macrocyclic ring.

  13. Comparison of the stability of Y-90-, Lu-177- and Ga-68- labeled human serum albumin microspheres (DOTA-HSAM)

    International Nuclear Information System (INIS)

    Introduction: Microparticles derived from denatured human serum albumin (DOTA-derivatized human serum albumin microspheres, or DOTA-HSAM) are attractive carriers of radionuclides for both therapeutic and diagnostic purposes. In this article, we describe a labeling procedure for diagnostic (Ga-68) and therapeutic (Y-90, Lu-177) radionuclides and report on the results of stability studies of these products. Methods: DOTA-HSAM was labeled in 0.5 M ammonium acetate buffer, pH 5.0, containing 0.02 mg/ml detergent. After adding the radionuclide, the mixture was shaken for 15 min at 90oC. Labeling yields and in vitro stability were determined by thin-layer chromatography. For determination of the in vivo stability of Ga-68 and Y-90 DOTA-HSAM, the particles were injected intravenously in Wistar rats. Results: Labeling yields up to 95% in the case of Ga-68 and Lu-177 were achieved. Ga-68-labeled DOTA-HSAM showed high in vitro and in vivo stability. The amount of particle-bound radioactivity of Lu-177 DOTA-HSAM declines slowly in a linear manner to approximately 72% after 13 days. For Y-90, the labeling yield decreased with increasing radioactivity level. We presume radiolysis as the reason for these findings. Conclusion: The labeling of DOTA-HSAM with different radionuclides is easy to perform. The radiation-induced cleavage of the labeled chelator together with the rather short half-life of radioactivity fixation in vivo (3.7 days) is, in our opinion, opposed to therapeutic applications of DOTA-HSAM. On the other hand, the high stability of Ga-68 DOTA-HSAM makes them an attractive candidate for the measurement of regional perfusion by PET.

  14. Preparation, quality control and biodistribution studies of [{sup 67}Ga]-DOTA-anti-CD20

    Energy Technology Data Exchange (ETDEWEB)

    Jalilian, A.R.; Khorrami, A. [Nuclear Science and Technology Research Inst., Karaj (IR). Nuclear Medicine Research Group, Agriculture, Medicine and Industrial Research School (AMIRS); Mirsadeghi, L.; Haji-Hosseini, R. [Payam-e-Noor Univ., Tehran (Iran). Biochemistry Dept.

    2008-07-01

    Rituximab was successively labeled with [{sup 67}Ga]-gallium chloride. The macrocyclic bifunctional chelating agent, N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 C using DOTA, N-hydroxy succinimide (NHS) in CH{sub 2}Cl{sub 2}. DOTA-Rituximab was obtained by the addition of 1 mL of a Rituximab pharmaceutical solution (5 mg/mL, in phosphate buffer, pH=7.8) to a glass tube pre-coated with DOTA-NHS (0.01-0.1 mg) at 25 C with continuous mild stirring for 15 h. Radiolabeling was performed at 37 C in 3 h. Radio-thin layer chromatography showed an overall radiochemical purity of 90%-95% at optimized conditions (specific activity = 30 GBq/mg, labeling efficacy; 82%). The final isotonic {sup 67}Ga-DOTA-rituximab complex was checked by gel electrophoresis for radiolysis. Radio-TLC was performed to ensure that only one species was present after filtration through a 0.22 {mu}m filter. Preliminary biodistribution studies in normal rat model performed to determine complex distribution of the radioimmunoconjugate up to 28 h. (orig.)

  15. Preparation, quality control and biodistribution studies of [67Ga]-DOTA-anti-CD20

    International Nuclear Information System (INIS)

    Rituximab was successively labeled with [67Ga]-gallium chloride. The macrocyclic bifunctional chelating agent, N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 C using DOTA, N-hydroxy succinimide (NHS) in CH2Cl2. DOTA-Rituximab was obtained by the addition of 1 mL of a Rituximab pharmaceutical solution (5 mg/mL, in phosphate buffer, pH=7.8) to a glass tube pre-coated with DOTA-NHS (0.01-0.1 mg) at 25 C with continuous mild stirring for 15 h. Radiolabeling was performed at 37 C in 3 h. Radio-thin layer chromatography showed an overall radiochemical purity of 90%-95% at optimized conditions (specific activity = 30 GBq/mg, labeling efficacy; 82%). The final isotonic 67Ga-DOTA-rituximab complex was checked by gel electrophoresis for radiolysis. Radio-TLC was performed to ensure that only one species was present after filtration through a 0.22 μm filter. Preliminary biodistribution studies in normal rat model performed to determine complex distribution of the radioimmunoconjugate up to 28 h. (orig.)

  16. Synthesis of DOTA-conjugated multimeric [Tyr3]octreotide peptides via a combination of Cu(I)-catalyzed "click" cycloaddition and thio acid/sulfonyl azide "sulfo-click" amidation and their in vivo evaluation.

    NARCIS (Netherlands)

    Yim, C.B.; Dijkgraaf, I.; Merkx, R.; Versluis, C.; Eek, A.; Mulder, G.E.; Rijkers, D.T.; Boerman, O.C.; Liskamp, R.M.

    2010-01-01

    Herein, we describe the design, synthesis, and biological evaluation of a series of DOTA-conjugated monomeric, dimeric, and tetrameric [Tyr(3)]octreotide-based analogues as a tool for tumor imaging and/or radionuclide therapy. These compounds were synthesized using a Cu(I)-catalyzed 1,3-dipolar cycl

  17. Brown coal derived products ameliorating soil acidity

    Energy Technology Data Exchange (ETDEWEB)

    Issa, J.; Patti, A.F.; Jackson, W.R. [Monash University, Clayton, Vic. (Australia). Centre for Green Chemistry

    2000-07-01

    Humic acid derived from brown coal, with added calcium, when applied to the soil surface, can increase pH deeper into the soil profile. The humates can move down with water percolating the soil. As they move down the added calcium bound to the humate's cation exchange sites (the acidic oxygen functional groups) can exchange with toxic aluminium ions and ions on exchange sites in the soil. Thus the soil pH is buffered, nutrient transport to plants assisted, and phytotoxic aluminium bound and rendered harmless to plants. K Humate is a commercially available source of humate (ex HRL Agriculture Pty Ltd Australia) derived from brown coal. It can be obtained by the treatment of brown coal with potassium hydroxide. Calsulmag is a commercial treated coal fly ash (also ex HRL Agriculture Pty Ltd) which can be used instead of lime due to its high inorganic calcium and magnesium content. When K humate and Calsulmag are combined in an aqueous mixture, and applied to the surface of an acidic soil, pH is increased (from 3.8 to 4.5) as is exchangeable calcium (30-50%), while exchangeable aluminium is decreased (30-50%), down to a 5 cm depth.

  18. Intracranial neoplasms: MR imaging with gadolinium - DOTA

    International Nuclear Information System (INIS)

    After a review of the capabilities of magnetic resonance without contrast in the diagnostic assessment of intracranial tumors, the authors report the literature and their own experience concerning the use of the paramagnetic contrast agent gadolinium-DOTA in MR imaging. A 0.5 T superconducting system (Toshiba MRT-50A) was used in the evaluation of these tumors. The intravenous administration of gadolinium-DOTA does not substantially increase the sensitivity of MR to primary intra-axial tumors. However, it may provide better delineation of tumor macroscopic extension and separation of the nidus from the surrounding edema. The presence of enhancement reflects areas of alteration of the blood brain barrier and may anticipate malignant changes at the histopathological examination. The role of gadolinium-DOTA administration for differentiation of intra-axial tumor recurrence from parenchyma changes induced by surgery or radiotherapy remains to be established. On the other hand, gadolinium-DOTA dramatically increases the sensitivity and specificity of MR in the investigation of extra-axial primary tumors (meningiomas, neurinomas), sellar tumors and secondary neoplastic lesions as well as in the investigation of their recurrence. Gadolinium-DOTA may be indirectly useful in the identification of the dysontogenetic tumors do not show enhancement as the low grade tumors do. (author)

  19. Robust labeling and comparative preclinical characterization of DOTA-TOC and DOTA-TATE

    International Nuclear Information System (INIS)

    Objectives: Various radionuclide-labeled somatostatin analogues are used currently for diagnosis and therapy of neuroendocrine tumors. In particular, [68Ga]Ga-DOTA-TOC is commonly used for diagnosis, while [177Lu]Lu-DOTA-TATE is used for therapy. With the development of theranostics and personalized medicine where the imaging diagnosis is tailored to the subsequent radiotherapy, it is of paramount importance to investigate the relevance of the ligand exchange. The aim of this study was to compare binding capacity of [67/68Ga]Ga-DOTA-TOC ([67/68Ga]Ga-N-(4,7,10-(tris(carboxymethyl)-1,4,7, 10-tetraazacyclododecan-1-yl) acetyl-D-Phe-c[Cys-D-Tyr-Trp-Lys-Thr-Cys]-Thr(ol)) and [67/68Ga]Ga-DOTA-TATE ([67/68Ga]Ga-N-(4,7,10-(tris(carboxymethyl)-1,4,7, 10-tetraazacyclododecan-1-yl)acetyl-D-Phe-c[Cys-D-Tyr-Trp-Lys-Thr-Cys]-Thr) in vitro in monkey brain cryosections and in vivo in the rat, where, in contrast to transfected cell lines, there is a heterogeneous distribution of somatostatin receptor (SSTR) subtypes. The influence of various production methods of [68Ga]Ga-DOTA-TOC and [68Ga]Ga-DOTA-TATE on the biological performance of the tracers was also studied. Material and Methods: [67Ga]Ga-DOTA-TOC, [68Ga]Ga-DOTA-TOC, [67Ga]Ga-DOTA-TATE and [68Ga]Ga-DOTA-TATE were synthesized including preconcentration and purification of the generator eluate. The binding of the radioligands was assessed in vitro using autoradiography on cryosections of Rhesus monkey brains and in vivo/ex vivo using organ distribution studies in rats. Results and Discussion: The tracer production method was improved in terms of higher robustness, simplification and good manufacturing practice (GMP) relevance. The synthesis variation did not influence the biological performance of the tracers. There was no statistically significant difference observed in the binding of [67/68Ga]Ga-DOTA-TOC and [67/68Ga]Ga-DOTA-TATE either in brain cortex in vitro or in rat biodistribution and uptake in SSTR-positive tissues

  20. 68Ga-DOTA-NOC somatostatin receptor-targeting imaging in pancreatic carcinoma

    International Nuclear Information System (INIS)

    Objective: To synthesize 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid-1-Nal3-octreotide (DOTA-NOC) as a new generation of positron emitting radionuclide labeled somatostatin analogue, and perform 68Ga-DOTA-NOC micro PET imaging on CFPAC-1 pancreatic cancer bearing nude mice. Methods: Thirty-seven MBq (100 μl) GaCl3 and 20 μg DOTA-NOC were added into 20 μl hydroxyethyl piperazine ethanesulfonic acid (HEPES) solution (0.1 mmol/L, pH=5.0), and heated for 15 min at 95 ℃. The radiochemical purity and in vitro stability of 68Ga-DOTA-NOC were analyzed with HPLC. Fifteen normal BALB/c mice were injected with 3.7 MBq 68Ga-DOTA-NOC via tail vein, and the biodistribution in dissected organs were measured at 5, 15, 30, 60 and 120 min respectively after the injection. CFPAC-1 pancreatic cancer cells were co-incubated with 68Ga-DOTA-NOC and the specific uptake ability was calculated. 68Ga-DOTA-NOC was injected into nude mice bearing CFPAC-1 tumors via tail vain. Dynamic and static images were performed by micro PET. ROI was drawn to calculate the T/NT and access TAC in tumor and main organs. The expression of SSTR (1-5) in CFPAC-1 cells in vivo was observed by flow cytometry. The correlation between the expression of SSTR and the T/NT was analyzed by linear correlation analysis. Results: 68Ga-NOTA-NOC had high radiolabeling yield of (98.8± 1.0)% and stability. Biodistribution study demonstrated that the predominant uptake of 68Ga-DOTA-NOC was found in the kidneys ((11.20±0.32) %ID/g at 5 min and (4.11±0.21) %ID/g at 60 min, respectively). The pancreas, lungs and stomach also showed high uptake. 68Ga-DOTA-NOC could be specifically uptaken by CFPAC-1 cells with high affinity. T/NT of 68Ga-DOTA-NOC in CFPAC-1 cancer xenografts was 3.2 ± 0.2 at 120 min post-injection. SSTR 1, 2, 4, 5 expressed in CFPAC-1 cells and xenograft tissues were (96.83± 1.23)%, (99.73±0.98)%, (90.42±0.63)% and (92.96±0.71)%, respectively. The SSTR 2, 5 expression level and

  1. 86Y-DOTA0-d-Phe1-Tyr3-octreotide (SMT487) - a phase 1 clinical study: pharmacokinetics, biodistribution and renal protective effect of different regimens of amino acid co-infusion

    International Nuclear Information System (INIS)

    The pharmacokinetics and dosimetry of 86Y-DOTA0-d-Phe1-Tyr3-octreotide (86Y-SMT487) were evaluated in a phase I positron emission tomography (PET) study of 24 patients with somatostatin receptor-positive neuroendocrine tumours. The effect of amino acid (AA) co-infusion on renal and tumour uptake was assessed in a cross-over randomised setting. Five regimens were tested: no infusion, 4-h infusion of 120 g mixed AA (26.4 g l-lysine + l-arginine), 4 h l-lysine (50 g), 10 h 240 g mixed AA (52.8 g l-lysine + l-arginine) and 4 h Lys-Arg (25 g each). Comparisons were performed on an intra-patient basis. Infusions of AA started 0.5 h prior to injection of 86Y-SMT487 and PET scans were obtained at 4, 24 and 48 h p.i. Absorbed doses to tissues were computed using the MIRD3 method. 86Y-SMT487 displayed rapid plasma clearance and exclusive renal excretion; uptake was noted in kidneys, tumours, spleen and, to a lesser extent, liver. The 4-h mixed AA co-infusion significantly (P86Y-SMT487 renal uptake by a mean of 21%. This protective effect was significant on the dosimetry data (3.3±1.3 vs 4.4±1.0 mGy/MBq; P90Y-SMT487 (maximum allowed dose: MAD) that would result in a 23-Gy cut-off dose to kidneys was calculated for each study: MAD was higher with mixed AA co-infusion by a mean of 46% (10-114%, P<0.05 vs no infusion). In comparison with 4 h mixed AA, the MAD was higher by a mean of 23% (9-37%; P<0.05) with prolonged infusion and by a mean of 16% (2-28%; P<0.05) with Lys-Arg. We conclude that infusion of large amounts of AA reduces renal exposure during peptide-based radiotherapy and allows higher absorbed doses to tumours. The prolongation of the infusion from 4 to 10 h further enhances the protective effect on the kidneys. (orig.)

  2. Preparation and biological studies of 68Ga-DOTA-alendronate

    OpenAIRE

    Ashraf Fakhari; Amir Jalilian; Fariba Johari-daha; Mehdi Shafiee-Ardestani; Ali Khalaj

    2016-01-01

    Objective(s): In line with previous research on the development of conjugated bisphosphonate ligands as new bone-avid agents, in this study, DOTA conjugated alendronate (DOTA-ALN) was synthesized and evaluated after labeling with gallium-68 (68Ga).Methods: DOTA-ALN was synthesized and characterized, followed by 68Ga-DOTA-ALN preparation, using DOTA-ALN and 68GaCl3 (pH: 4-5) at 92-95°C for 10 min. Stability tests, hydroxyapatite assay, partition coefficient calculation,biodistribution studies,...

  3. 68Ga-autoclabeling of DOTA-TATE and DOTA-NOC

    DEFF Research Database (Denmark)

    Blom, Elisabeth; Koziorowski, Jacek

    2012-01-01

    A new method combining (68)Ga-labeling and steam sterilization, here called autoclabeling, has been evaluated for two somatostatin receptor binding tracers used for positron emission tomography (PET) imaging of neuroendocrine tumors; DOTA-TATE and -NOC.......A new method combining (68)Ga-labeling and steam sterilization, here called autoclabeling, has been evaluated for two somatostatin receptor binding tracers used for positron emission tomography (PET) imaging of neuroendocrine tumors; DOTA-TATE and -NOC....

  4. Assessment of blood flow with 68Ga-DOTA PET in experimental inflammation: a validation study using 15O-water

    OpenAIRE

    Autio, Anu; Saraste, Antti; Kudomi, Nobuyuki; Saanijoki, Tiina; Johansson, Jarkko; Liljenbäck, Heidi; Tarkia, Miikka; Oikonen, Vesa; Sipilä, Hannu T; Roivainen, Anne

    2014-01-01

    Increased blood flow and vascular permeability are key events in inflammation. Based on the fact that Gadolinium-1,4,7,10-tetraazacyclododecane-N,N‘,N‘‘,N‘‘‘-tetraacetic acid (Gd-DOTA) is commonly used in magnetic resonance (MR) imaging of blood flow (perfusion), we evaluated the feasibility of its Gallium-68 labeled DOTA analog (68Ga-DOTA) for positron emission tomography (PET) imaging of blood flow in experimental inflammation. Adult, male Sprague-Dawley rats with turpentine oil induced ste...

  5. Synthesis and evaluation of 68Ga-labeled DOTA-2-deoxy-D-glucosamine as a potential radiotracer in μPET imaging

    OpenAIRE

    Yang, Zhi; Xiong, Chiyi; Zhang, Rui; Zhu, Hua; Li, Chun

    2012-01-01

    The purposes of this study were to develop an efficient method of labeling D-glucosamine hydrochloride with gallium 68 (68Ga) and investigate the imaging properties of the resulting radiotracer in a human tumor xenograft model using micro-positron emission tomography (μPET). The precursor compound 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-2-deoxy-D-glucosamine (DOTA-DG) was synthesized from D-glucosamine hydrochloride and 2-(4-isothiocyanatobenzyl)-DOTA. Radiolabeling of...

  6. 68Ga-DOTA-NGR as a novel molecular probe for APN-positive tumor imaging using MicroPET

    International Nuclear Information System (INIS)

    Aminopeptidase N (APN) is selectively expressed on many tumors and the endothelium of tumor neovasculature, and may serve as a promising target for cancer diagnosis and therapy. Asparagine–glycine–arginine (NGR) peptides have been shown to bind specifically to the APN receptor and have served as vehicles for the delivery of various therapeutic drugs in previous studies. The purpose of this study was to synthesize and evaluate the efficacy of a 68Ga-labeled NGR peptide as a new molecular probe that binds to APN. Methods: NGR peptide was conjugated with 1,4,7,10-tetraazacyclododecane-N,N’,N”,N”’-tetraacetic acid (DOTA) and labeled with 68Ga at 95 °C for 10 min. In vitro uptake and binding analysis was performed with A549 and MDA-MB231 cells. Biodistribution of 68Ga-DOTA-NGR was determined in normal mice by dissection method. 68Ga-DOTA-NGR PET was performed in A549 and MDA-MB231 xenografts, and included dynamic and static imaging. APN expression in tumors and new vasculatures was analyzed by immunohistochemistry. Results: The radiochemical purity of 68Ga-DOTA-NGR was 98.0% ± 1.4% with a specific activity of about 17.49 MBq/nmol. The uptake of 68Ga-DOTA-NGR in A549 cells increased with longer incubation times, and could be blocked by cold DOTA-NGR, while no specific uptake was found in MDA-MB231 cells. In vivo biodistribution studies showed that 68Ga-DOTA-NGR was mainly excreted from the kidney, and rapidly cleared from blood and nonspecific organs. MicroPET imaging showed that high focal accumulation had occurred in the tumor site at 1 h post-injection (pi) in A549 tumor xenografts. A significant reduction of tumor uptake was observed following coinjection with a blocking dose of DOTA-NGR, whereas only mild uptake was found in MDA-MB231 tumor xenografts. Tumor uptake, measured as the tumor/lung ratio, increased with time peaking at 12.58 ± 1.26 at 1.5 h pi. Immunohistochemical staining confirmed that APN was overexpressed on A549 cells and

  7. [64Cu]-Labelled Trastuzumab: Optimisation of Labelling by DOTA and NODAGA Conjugation and Initial Evaluation in Mice

    DEFF Research Database (Denmark)

    Schjøth-Eskesen, Christina; Nielsen, Carsten Haagen; Heissel, Søren;

    2015-01-01

    The human epidermal growth factor receptor-2 (HER2) is overexpressed in 20-30% of all breast cancer cases, leading to increased cell proliferation, growth and migration. The monoclonal antibody, trastuzumab, binds to HER2 and is used for treatment of HER2-positive breast cancer. Trastuzumab has...... previously been labelled with copper-64 by conjugation of a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator. The aim of this study was to optimise the (64) Cu-labelling of DOTA-trastuzumab and as the first to produce and compare with its 1,4,7-triazacyclononane, 1-glutaric acid-5...

  8. Caffeic acid derivatives in the roots of yacon (Smallanthus sonchifolius).

    Science.gov (United States)

    Takenaka, Makiko; Yan, Xiaojun; Ono, Hiroshi; Yoshida, Mitsuru; Nagata, Tadahiro; Nakanishi, Tateo

    2003-01-29

    Five caffeic acid derivatives were found in the roots of yacon, Smallanthus sonchifolius (Poepp. and Endl.) H. Robinson, Asteraceae, as the major water-soluble phenolic compounds. The structures of these compounds were determined by analysis of spectroscopic data. Two of these were chlorogenic acid (3-caffeoylquinic acid) and 3,5-dicaffeoylquinic acid, common phenolic compounds in plants of the family Asteraceae. Three were esters of caffeic acid with the hydroxy groups of aldaric acid, derived from hexose. The structure of the aldaric moiety was determined by hydrolysis and comparison of NMR spectra with those of standard aldaric acids. The compounds were novel caffeic acid esters of altraric acid: 2,4- or 3,5-dicaffeoylaltraric acid, 2,5-dicaffeoylaltraric acid, and 2,3,5- or 2,4,5-tricaffeoylaltraric acid. PMID:12537459

  9. Rapid intracerebroventricular delivery of Cu-DOTA-etanercept after peripheral administration demonstrated by PET imaging

    Directory of Open Access Journals (Sweden)

    Chen Xiaoyuan

    2009-02-01

    Full Text Available Abstract Background The cytokines interleukin-1 and tumor necrosis factor (TNF, and the cytokine blocker interleukin-1 receptor antagonist, all have been demonstrated to enter the cerebrospinal fluid (CSF following peripheral administration. Recent reports of rapid clinical improvement in patients with Alzheimer's disease and related forms of dementia following perispinal administration of etanercept, a TNF antagonist, suggest that etanercept also has the ability to reach the brain CSF. To investigate, etanercept was labeled with a positron emitter to enable visualization of its intracranial distribution following peripheral administration by PET in an animal model. Findings Radiolabeling of etanercept with the PET emitter 64Cu was performed by DOTA (1,4,7,10-tetraazadodecane-N,N',N",N"'-tetraacetic acid conjugation of etanercept, followed by column purification and 64Cu labeling. MicroPET imaging revealed accumulation of 64Cu-DOTA-etanercept within the lateral and third cerebral ventricles within minutes of peripheral perispinal administration in a normal rat anesthesized with isoflurane anesthesia, with concentration within the choroid plexus and into the CSF. Conclusion Synthesis of 64Cu-DOTA-etanercept enabled visualization of its intracranial distribution by microPET imaging. MicroPET imaging documented rapid accumulation of 64Cu-DOTA-etanercept within the choroid plexus and the cerebrospinal fluid within the cerebral ventricles of a living rat after peripheral administration. Further study of the effects of etanercept and TNF at the level of the choroid plexus may yield valuable insights into the pathogenesis of Alzheimer's disease.

  10. The Adsorption Effect of Quaternized Chitosan Derivatives on Bile Acid

    Institute of Scientific and Technical Information of China (English)

    Shu Xian MENG; Ya Qing FENG; Wen Jin LI; Cai Xia YIN; Jin Ping DENG

    2006-01-01

    Three quaternized chitosan derivatives were synthesized and their adsorption performance of bile acid from aqueous solution was studied. The adsorption capacities and rates of bile acid onto quaternized chitosan derivatives were evaluated. The kinetic experimental data properly correlated with the second-order kinetic model, which indicated that the chemical sorption is the rate-limiting step. The results showed that the quaternized chitosan derivatives are favorable adsorbents for bile acid.

  11. Selenium- or tellurium- containing bile acids and derivatives thereof

    International Nuclear Information System (INIS)

    This invention relates to the preparation of selenium and tellurium derivatives, particularly γ-emitting radioactive derivatives of bile acids and bile salts. Such compounds are valuable in the examination of body function, especially small bowel function. (author)

  12. Synthesis and antitumor activity of derivatives of 23-hydroxybetulinic acid

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A series of natural product 23-hydroxybetulinic acid derivatives were prepared. In the preparation of mono-O-benzoyl ester derivative, it was observed that benzoyl group migrated from 3-O- to 23-O-position during the detritylation.

  13. Engineering an antibody with picomolar affinity to DOTA chelates of multiple radionuclides for pretargeted radioimmunotherapy and imaging

    Energy Technology Data Exchange (ETDEWEB)

    Orcutt, Kelly Davis; Slusarczyk, Adrian L. [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Cieslewicz, Maryelise [Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Ruiz-Yi, Benjamin [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Bhushan, Kumar R. [Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Frangioni, John V. [Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Wittrup, K. Dane, E-mail: wittrup@mit.ed [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

    2011-02-15

    Introduction: In pretargeted radioimmunotherapy (PRIT), a bifunctional antibody is administered and allowed to pre-localize to tumor cells. Subsequently, a chelated radionuclide is administered and captured by cell-bound antibody while unbound hapten clears rapidly from the body. We aim to engineer high-affinity binders to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelates for use in PRIT applications. Methods: We mathematically modeled antibody and hapten pharmacokinetics to analyze hapten tumor retention as a function of hapten binding affinity. Motivated by model predictions, we used directed evolution and yeast surface display to affinity mature the 2D12.5 antibody to DOTA, reformatted as a single chain variable fragment (scFv). Results: Modeling predicts that for high antigen density and saturating bsAb dose, a hapten-binding affinity of 100 pM is needed for near-maximal hapten retention. We affinity matured 2D12.5 with an initial binding constant of about 10 nM to DOTA-yttrium chelates. Affinity maturation resulted in a 1000-fold affinity improvement to biotinylated DOTA-yttrium, yielding an 8.2{+-}1.9 picomolar binder. The high-affinity scFv binds DOTA complexes of lutetium and gadolinium with similar picomolar affinity and indium chelates with low nanomolar affinity. When engineered into a bispecific antibody construct targeting carcinoembryonic antigen, pretargeted high-affinity scFv results in significantly higher tumor retention of a {sup 111}In-DOTA hapten compared to pretargeted wild-type scFv in a xenograft mouse model. Conclusions: We have engineered a versatile, high-affinity, DOTA-chelate-binding scFv. We anticipate it will prove useful in developing pretargeted imaging and therapy protocols to exploit the potential of a variety of radiometals.

  14. Engineering an antibody with picomolar affinity to DOTA chelates of multiple radionuclides for pretargeted radioimmunotherapy and imaging

    International Nuclear Information System (INIS)

    Introduction: In pretargeted radioimmunotherapy (PRIT), a bifunctional antibody is administered and allowed to pre-localize to tumor cells. Subsequently, a chelated radionuclide is administered and captured by cell-bound antibody while unbound hapten clears rapidly from the body. We aim to engineer high-affinity binders to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelates for use in PRIT applications. Methods: We mathematically modeled antibody and hapten pharmacokinetics to analyze hapten tumor retention as a function of hapten binding affinity. Motivated by model predictions, we used directed evolution and yeast surface display to affinity mature the 2D12.5 antibody to DOTA, reformatted as a single chain variable fragment (scFv). Results: Modeling predicts that for high antigen density and saturating bsAb dose, a hapten-binding affinity of 100 pM is needed for near-maximal hapten retention. We affinity matured 2D12.5 with an initial binding constant of about 10 nM to DOTA-yttrium chelates. Affinity maturation resulted in a 1000-fold affinity improvement to biotinylated DOTA-yttrium, yielding an 8.2±1.9 picomolar binder. The high-affinity scFv binds DOTA complexes of lutetium and gadolinium with similar picomolar affinity and indium chelates with low nanomolar affinity. When engineered into a bispecific antibody construct targeting carcinoembryonic antigen, pretargeted high-affinity scFv results in significantly higher tumor retention of a 111In-DOTA hapten compared to pretargeted wild-type scFv in a xenograft mouse model. Conclusions: We have engineered a versatile, high-affinity, DOTA-chelate-binding scFv. We anticipate it will prove useful in developing pretargeted imaging and therapy protocols to exploit the potential of a variety of radiometals.

  15. Somatostatin-based radiopeptide therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in neuroendocrine tumours

    International Nuclear Information System (INIS)

    Somatostatin-based radiopeptide treatment is generally performed using the β-emitting radionuclides 90Y or 177Lu. The present study aimed at comparing benefits and harms of both therapeutic approaches. In a comparative cohort study, patients with advanced neuroendocrine tumours underwent repeated cycles of [90Y-DOTA]-TOC or [177Lu-DOTA]-TOC until progression of disease or permanent adverse events. Multivariable Cox regression and competing risks regression were employed to examine predictors of survival and adverse events for both treatment groups. Overall, 910 patients underwent 1,804 cycles of [90Y-DOTA]-TOC and 141 patients underwent 259 cycles of [177Lu-DOTA]-TOC. The median survival after [177Lu-DOTA]-TOC and after [90Y-DOTA]-TOC was comparable (45.5 months versus 35.9 months, hazard ratio 0.91, 95 % confidence interval 0.63-1.30, p = 0.49). Subgroup analyses revealed a significantly longer survival for [177Lu-DOTA]-TOC over [90Y-DOTA]-TOC in patients with low tumour uptake, solitary lesions and extra-hepatic lesions. The rate of severe transient haematotoxicities was lower after [177Lu-DOTA]-TOC treatment (1.4 vs 10.1 %, p = 0.001), while the rate of severe permanent renal toxicities was similar in both treatment groups (9.2 vs 7.8 %, p = 0.32). The present results revealed no difference in median overall survival after [177Lu-DOTA]-TOC and [90Y-DOTA]-TOC. Furthermore, [177Lu-DOTA]-TOC was less haematotoxic than [90Y-DOTA]-TOC. (orig.)

  16. Experimental MR imaging with Gd-DOTA: Preliminary results

    International Nuclear Information System (INIS)

    To evaluate the paramagnetic properties of a new gadolinium chelate, Gd-DOTA, in vitro and in vivo MR imaging was performed with a 0.5-T supraconductive magnet. The in vitro study consisted in measuring the MR signal obtained with various concentrations of Gd-DOTA and Gd-DTPA in different solutions. Potentialization of the paramagnetic properties of both DOTA and DTPA can be achieved by deuterium, glycerol, and protein solutions. The in vivo study was performed in rabbits with various experimental lesions. Enhancement of anatomic details was obtained with both Gd-DOTA and Gd-DTPA. There was no significant difference between Gd-DOTA and Gd-DTPA, both for in vitro and in vivo experiments. Gd-DOTA appears to be a potential paramagnetic agent for MR imaging

  17. Development of 177Lu-DOTA-anti-CD20 for radioimmunotherapy

    International Nuclear Information System (INIS)

    Rituximab was successively labeled with 177Lu-lutetium chloride. 177Lu chloride was obtained by thermal neutron flux (4 x 1013 n cm-2 s-1) of natural Lu2O3 sample with a specific activity of 2.6-3 GBq/mg. The macrocyclic bifunctional chelating agent, N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 deg C using DOTA, N-hydroxy succinimide (NHS) in CH2Cl2. DOTA-rituximab was obtained by the addition of 1 mL of a rituximab pharmaceutical solution (5 mg/mL, in phosphate buffer, pH 7.8) to a glass tube pre-coated with DOTA-NHS (0.01-0.1 mg) at 25 deg C with continuous mild stirring for 15 h. Radiolabeling was performed at 37 deg C in 24 h. Radio-thin layer chromatography showed an overall radiochemical purity of >98% at optimized conditions (specific activity = 444 MBq/mg, labeling efficacy; 82%). The final isotonic 177Lu-DOTA-rituximab complex was checked by gel electrophoresis for structure integrity control. Radio-TLC was performed to ensure that only one species was present after filtration through a 0.22 μm filter. Preliminary biodistribution studies in normal rats were carried out to determine complex distribution of the radioimmunoconjugate up to 168 h. The biodistribution data were in accordance with other antiCD20 radioimmunoconjugates already reported. (author)

  18. Preparation and Preliminary Biological Evaluation of {sup 177}Lu-DOTA folate as Potential Folate Receptor Targeting Therapeutic Agent

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Kang-Hyuk; Hong, Young-Don; Pyun, Mi-Sun; Lee, So-Young; Felipe, Fenelope; Yoon, Sun-Ha; Choi, Sun-Ju [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2008-10-15

    Folic Acid (FA) and FA derivatives are overexpressed on several tumor cells. The cell-membrane folic acid receptors are known to be responsible for the cellular accumulation of FA and FA analogs, such as methotrexate and folic acid. Folate has been characterized to have high affinity for the folate-receptor positive cells and tissues and considered to be useful as diagnostic imaging and therapeutic agent. In 1940s, Folate analogue, aminopterin, was first used for treatment of leukemia and recently, many folate derivatives were tried for cancer-treatment agent as well as visualization of folate receptor. Many researchers tried to conjugate folic acid with macromolecules or low molecular weight chelators through its alpha or gamma carboxylate. However, despite the reduced binding affinity, FAs are still recognized by the folate receptor. Therefore, we focused to develop folate-based radiopharmaceutical that has the potential to be used as a therapeutic agent. We report here the synthesis and the radiolabeling of {sup 177}Lu-DOTA as well as the biodistribution data of our developed compound.

  19. Synthesis and Characterization of α-HexadecyI-DOTA and its Gd(Ⅲ) Chelate

    Institute of Scientific and Technical Information of China (English)

    FENG,Zhi-Ming,(冯志明); LI,Feng(李峰); LEl,Chun-Hua(雷春华); CHEN,Ronga(陈蓉); LI,Xiao-Ru(李晓如)

    2004-01-01

    Synthesis and characterization of the ligand,10-(a-hexadecylcarboxymethyl)-1,4,7,10-tetraazacyclododecane1,4,7-triacetic acid (H4L),and its Gd(Ⅲ) chelate are described.Protonation constants for H4L ( lg KHi= 10.52,9.45,4.74,4.10) and the stability constant for GdL (lg KGdL- =24.50) were determined by potentiometric titrations.The results obtained show that the ligand still maintains the strong chelating properties of the parent DOTA (1,4,7,10-tetraazacyclododecane-N,N',N"N'"-tetraacetic acid) after introduction of a linear chain hexadecyl group at the acetic side chain of DOTA,and its basicity is not significantly altered.

  20. Determination of Ascorbic Acid in Vegetables by Derivative Spectrophotometry

    OpenAIRE

    Aydoğmuş, Zeynep; ÇETİN, Sevil Müge

    2002-01-01

    Determination of ascorbic acid (AA) in garlic, green pepper and chestnut was performed by derivative spectrophotometry without using any pre-separation or background correction techniques. The method is based on the measurement of the distances between two extremum values (peak-to-peak amplitudes) in second and third order derivative spectra of the extracts. Ten percent trichloroacetic acid was found to be the most suitable extraction solution. In the second order derivative spectru...

  1. Acetylcholinesterase inhibitory properties of some benzoic acid derivatives

    Science.gov (United States)

    Yildiz, Melike; Kiliç, Deryanur; Ünver, Yaǧmur; Şentürk, Murat; Askin, Hakan; Küfrevioǧlu, Ömer Irfan

    2016-04-01

    Acetylcholinesterase (AChE) hydrolyses the neurotransmitter acetylcholine to acetic acid and choline. AChE inhibitors are used in treatment of several neurodegeneartive disorder and Alzheimer's disease. In the present study, inhibition of AChE with some benzoic acid derivatives were investigated. 3-Chloro-benzoic acid (1), 2-hydroxy-5-sulfobenzoic acid (2), 2-(sulfooxy) benzoic acid (3), 2-hydroxybenzoic acid (4), 2,3-dimethoxybenzoic (5), and 3,4,5-trimethoxybenzoic (6) were calculated IC50 values AChE enzyme. Kinetic investigations showed that similarly to AChE inhibitors. Benzoic acid derivatives (1-6) investigated are encouraging agents which may be used as lead molecules in order to derivative novel AChE inhibitors that might be useful in medical applications.

  2. Natural Cinnamic Acids, Synthetic Derivatives and Hybrids with Antimicrobial Activity

    Directory of Open Access Journals (Sweden)

    Juan David Guzman

    2014-11-01

    Full Text Available Antimicrobial natural preparations involving cinnamon, storax and propolis have been long used topically for treating infections. Cinnamic acids and related molecules are partly responsible for the therapeutic effects observed in these preparations. Most of the cinnamic acids, their esters, amides, aldehydes and alcohols, show significant growth inhibition against one or several bacterial and fungal species. Of particular interest is the potent antitubercular activity observed for some of these cinnamic derivatives, which may be amenable as future drugs for treating tuberculosis. This review intends to summarize the literature data on the antimicrobial activity of the natural cinnamic acids and related derivatives. In addition, selected hybrids between cinnamic acids and biologically active scaffolds with antimicrobial activity were also included. A comprehensive literature search was performed collating the minimum inhibitory concentration (MIC of each cinnamic acid or derivative against the reported microorganisms. The MIC data allows the relative comparison between series of molecules and the derivation of structure-activity relationships.

  3. Synthesis of azo derivatives of 4-aminosalicylic acid

    Institute of Scientific and Technical Information of China (English)

    Zheng Bao Zhao; Hui Xia Zheng; Yuan Gui Wei; Jiang Liu

    2007-01-01

    For searching a better 4-aminosalicylic acid derivative with higher activity and less side effects against the inflammatory bowel disease, 4-aminosalicylic acid (4-ASA) was protected by benzyloxycarbonyl and acetyl, respectively.The resultant was hydrogenized to remove protective group of amino group, then the product was reacted with NaNO2 to give diazonium salt, which was conjugated with salicylic acid, hydroxybenzene, N-salicyloyl glycine acid to get azo derivatives of 4-ASA.The azo derivatives were hydrolyzed under the alkaline condition to get the target products.All compounds were characterized by FT-IR, 1H NMR, 13C NMR spectra in details.New derivatives of 4-ASA were characterized.The synthetic route was reasonable and feasible.

  4. Amifostine protects rat kidneys during peptide receptor radionuclide therapy with [177Lu-DOTA0,Tyr3]octreotate

    International Nuclear Information System (INIS)

    In peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues, the kidneys are the major dose-limiting organs, because of tubular reabsorption and retention of radioactivity. Preventing renal uptake or toxicity will allow for higher tumour radiation doses. We tested the cytoprotective drug amifostine, which selectively protects healthy tissue during chemo- and radiotherapy, for its renoprotective capacities after PRRT with high-dose [177Lu-DOTA0,Tyr3]octreotate. Male Lewis rats were injected with 278 or 555 MBq [177Lu-DOTA0,Tyr3]octreotate to create renal damage and were followed up for 130 days. For renoprotection, rats received either amifostine or co-injection with lysine. Kidneys, blood and urine were collected for toxicity measurements. At 130 days after PRRT, a single-photon emission computed tomography (SPECT) scan was performed to quantify tubular uptake of 99mTc-dimercaptosuccinic acid (DMSA), a measure of tubular function. Treatment with 555 MBq [177Lu-DOTA0,Tyr3]octreotate resulted in body weight loss, elevated creatinine and proteinuria. Amifostine and lysine treatment significantly prevented this rise in creatinine and the level of proteinuria, but did not improve the histological damage. In contrast, after 278 MBq [177Lu-DOTA0,Tyr3]octreotate, creatinine values were slightly, but not significantly, elevated compared with the control rats. Proteinuria and histological damage were different from controls and were significantly improved by amifostine treatment. Quantification of 99mTc-DMSA SPECT scintigrams at 130 days after [177Lu-DOTA0,Tyr3]octreotate therapy correlated well with 1/creatinine (r 2 = 0.772, p 177Lu-DOTA0,Tyr3]octreotate. Besides lysine, amifostine might be used in clinical PRRT as well as to maximise anti-tumour efficacy. (orig.)

  5. Radiolabelling, quality control and radiochemical purity assessment of the Octreotide analogue {sup 68}Ga DOTA NOC

    Energy Technology Data Exchange (ETDEWEB)

    Di Pierro, D.; Rizzello, A. [PET Radiopharmacy-Nuclear Medicine, Azienda Ospedaliero, Universitaria di Bologna, S. Orsolo-Malpighi Hospital, Via Massarenti 9, 40318 Bologna (Italy); Cicoria, G. [Medical Physics, Azienda Ospedaliero, Universitaria di Bologna, S. Orsolo-Malpighi Hospital, Via Massarenti 9, 40318 Bologna (Italy); Lodi, F. [PET Radiopharmacy-Nuclear Medicine, Azienda Ospedaliero, Universitaria di Bologna, S. Orsolo-Malpighi Hospital, Via Massarenti 9, 40318 Bologna (Italy); Marengo, M.; Pancaldi, D. [Medical Physics, Azienda Ospedaliero, Universitaria di Bologna, S. Orsolo-Malpighi Hospital, Via Massarenti 9, 40318 Bologna (Italy); Trespidi, S. [PET Radiopharmacy-Nuclear Medicine, Azienda Ospedaliero, Universitaria di Bologna, S. Orsolo-Malpighi Hospital, Via Massarenti 9, 40318 Bologna (Italy); Boschi, S. [PET Radiopharmacy-Nuclear Medicine, Azienda Ospedaliero, Universitaria di Bologna, S. Orsolo-Malpighi Hospital, Via Massarenti 9, 40318 Bologna (Italy)], E-mail: stefano.boschi@aosp.bo.it

    2008-08-15

    Somatostatin receptors 1-5 are over expressed in neuroendocrine tumours (NETs). {sup 68}Ga-labelled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-Octreotide (DOTA NOC), a recent synthesized somatostatin analogue, shows high affinity for those receptors. Herein, modifications of a commercial module for the labelling of DOTA NOC with {sup 68}Ga, as well as the assessment of time course of the radiochemical purity variation are described. The evaluation of radiochemical stability was done by two different chromatographic methods: reversed-phase radio HPLC and fast TLC analysis. Labelled compound has been found radiochemically stable within 3 h from the end of labelling (EOL) and radiochemical purity was always higher than 99%. After 73 labelling sessions the system showed great reproducibility and high radiochemical yield.

  6. Determination of peptide content and purity of DOTA-peptides by metal ion titration and UPLC. An alternative method to monitor quality of DOTA-peptides

    International Nuclear Information System (INIS)

    PRRT requires high specific activities, thus at low molar ratio between DOTA-peptide and radioactivity. Therefore, the ingredients of the reaction, including (radio)metals and DOTA-peptide must be pure and the content known. Our aim was to quantify content and purity of DOTA-peptide by a base-to-base separation of DOTA-peptide and metal-DOTA-peptide by UPLC and UV-detection. Quantification of these peaks reveals an accurate and sensitive method to quantify purity and content of DOTA-peptides. Moreover, this technique enables monitoring of the (radio)labeling process and co-introduction of impurities, including metal ions. (author)

  7. Single vial kit formulation for preparation of PET radiopharmaceutical. 68Ga-DOTA-TOC

    International Nuclear Information System (INIS)

    This paper describes the development of a lyophilized cold kit of DOTA-[Tyr3]-Octreotide (DOTA-TOC) for instant compounding of 68Ga-DOTA-TOC, suitable for diagnosis of neuroendocrine tumors. The work involved formulation of DOTA-TOC kits, optimization of radiolabeling, quality control of 68Ga-DOTA-TOC and animal biodistribution studies. The prepared kits enable a reliable method for preparation of 68Ga-DOTA-TOC of high radiochemical purity and excellent stability. Availability of such kits along with 68Ge/68Ga generators is expected to stimulate the widespread use of 68Ga-DOTA-TOC in nuclear medicine practice in developing countries. (author)

  8. Yhteisöpalvelu Dota 2 -pelille

    OpenAIRE

    Peltonen, Markus

    2014-01-01

    Opinnäytetyössä toteutettiin suomalaisille Dota 2 -pelin pelaajille tai pelistä kiin-nostuneille yhteisöportaali, josta voidaan seurata portaalin kautta käytyjen pelien tilastoja, järjestää pienimuotoisia turnauksia tai katsoa reaaliaikaista pelikuvaa käynnissä olevista peleistä tai pelialan tapahtumista. Tavoitteena oli laatia asiakkaan toiveiden mukainen yhteisöportaali, jota käyttäjän olisi myös helppo ylläpitää. Portaali toteutettiin Drupal 7 -sisällönhallintajärjestelmää käyttäen. Dr...

  9. Hydrophobicity and Retention Coefficient of Selected Bile Acid Oxo Derivatives

    NARCIS (Netherlands)

    Posa, Mihalj; Pilipovic, Ana; Lalic, Mladena; Popovic, Jovan

    2010-01-01

    Retention coefficients (k) of cholic acid and its keto derivatives are determined by means of Reversed Phase High Pressure Liquid Chromatography at different temperatures (303K, 309K, and 313K). At each studied temperature, retention factor decreases if the hydroxyl group in the cholic acid molecule

  10. Amino acid derived 1,4-dialkyl substituted imidazolones

    DEFF Research Database (Denmark)

    Diness, Frederik; Meldal, Morten Peter

    2010-01-01

    A general method for synthesis of 1,4-substituted imidazolones from amino acids on solid support or in solution has been developed. Amino acid derived 3-Boc-(1,3)-oxazinane (Box) protected amino aldehyde building blocks were coupled through urea bonds to the amino terminal of dipeptides or amino ...

  11. Caffeic Acid Derivatives in Dried Lamiaceae and Echinacea purpurea Products

    Science.gov (United States)

    The concentrations of caffeic acid derivatives within Lamiaceae and Echinacea (herb, spice, tea, and dietary supplement forms) readily available in the U.S. marketplace (n=72) were determined. After the first identification of chicoric acid in Ocimum basilicum (basil), the extent to which chicoric a...

  12. Comparison of DOTA and NODAGA as chelators for 64Cu-labeled immunoconjugates

    International Nuclear Information System (INIS)

    Introduction: Bifunctional chelators have been shown to impact the biodistribution of monoclonal antibody (mAb)-based imaging agents. Recently, radiolabeled 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA)-peptide complexes have demonstrated improved in vivo stability and performance compared to their 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) counterparts. Here, we investigated if similar utility could be achieved with mAbs and compared 64Cu-labeled DOTA and NODAGA-immunoconjugates for the detection of epithelial cell adhesion molecule (EpCAM) in a prostate cancer model. Methods: DOTA and NODAGA-immunoconjugates of an EpCAM targeting mAb (mAb7) were synthesized and radiolabeled with 64Cu (DOTA: 40 °C for 1 hr; NODAGA: 25 °C for 1 hr). The average number of chelators per mAb was quantified by isotopic dilution, and the biological activity of the immunoconjugates was evaluated by flow cytometry and ELISA. Radioligand assays were performed to compare cellular uptake and determine the dissociation constant (Kd) and maximum number of binding sites (Bmax) for the immunoconjugates using DsRed-transfected PC3-cells. A PC3-DsRed xenograft tumor model was established in nude mice and used to perform biodistribution studies to compare organ uptake and pharmacokinetics. Results: 64Cu-DOTA-mAb7 and 64Cu-NODAGA-mAb7 were prepared with chelator/protein ratios of 2–3 and obtained in comparable radiochemical yields ranging from 59 to 71%. Similar immunoreactivity was observed with both agents, and mock labeling studies indicated that incubation at room temperature or 40 °C did not affect potency. 64Cu-NODAGA-mAb7 demonstrated higher in vitro cellular uptake while 64Cu-DOTA-mAb7 had higher Kd and Bmax values. From the biodistribution data, we found similar tumor uptake (13.44 ± 1.21%ID/g and 13.24 ± 4.86%ID/g for 64Cu-DOTA-mAb7 and 64Cu-NODAGA-mAb7, respectively) for both agents at 24 hr, although normal prostate tissue was significantly

  13. In Vitro Cytotoxicity of Low-Dose-Rate Radioimmunotherapy by the Alpha-Emitting Radioimmunoconjugate Thorium-227-DOTA-Rituximab

    International Nuclear Information System (INIS)

    Purpose: To determine whether the low-dose-rate α-particle-emitting radioimmunoconjugate 227Th-1,4,7,10-p-isothiocyanato-benzyl-tetraazacyclododecane-1,4,7, 10-tetraacetic acid (DOTA)-rituximab can be used to inactivate lymphoma cells growing as single cells and small colonies. Methods and Materials: CD20-positive lymphoma cell lines were treated with 227Th-DOTA-rituximab for 1-5 weeks. To simulate the in vivo situation with continuous but decreasing supply of radioimmunoconjugates from the blood pool, the cells were not washed after incubation with 227Th-DOTA-rituximab, but half of the medium was replaced with fresh medium, and cell concentration and cell-bound activity were determined every other day after start of incubation. A microdosimetric model was established to estimate the average number of hits in the nucleus for different localizations of activity. Results: There was a specific targeted effect on cell growth of the 227Th-DOTA-rituximab treatment. Although the cells were not washed after incubation with 227Th-DOTA-rituximab, the average contribution of activity in the medium to the mean dose was only 6%, whereas the average contribution from activity on the cells' own surface was 78%. The mean dose rates after incubation with 800 Bq/mL 227Th-DOTA-rituximab varied from 0.01 to 0.03 cGy/min. The average delay in growing from 105 to 107 cells/mL was 15 days when the cells were treated with a mean absorbed radiation dose of 2 Gy α-particle radiation from 227Th-DOTA-rituximab, whereas it was 11 days when the cells were irradiated with 6 Gy of X-radiation. The relative biologic effect of the treatment was estimated to be 2.9-3.4. Conclusions: The low-dose-rate radioimmunoconjugate 227Th-DOTA-rituximab is suitable for inactivation of single lymphoma cells and small colonies of lymphoma cells.

  14. A comparison of 111In- or 64Cu-DOTA-trastuzumab Fab fragments for imaging subcutaneous HER2-positive tumor xenografts in athymic mice using microSPECT/CT or microPET/CT

    OpenAIRE

    Chan, Conrad; Scollard, Deborah A; McLarty, Kristin; Smith, Serena; Reilly, Raymond M

    2011-01-01

    Background Our objective was to compare 111In- or 64Cu-DOTA-trastuzumab Fab fragments for imaging small or large s.c. tumor xenografts in athymic mice that display a wide range of human epidermal growth factor receptor-2 (HER2) expression using microSPECT/CT or microPET/CT. Methods Trastuzumab Fab were labeled with 111In or 64Cu by conjugation to 1,4,7,10-tetraazacyclododecane N, N', N'', N'''-tetraacetic acid (DOTA). The purity of 111In- and 64Cu-DOTA-trastuzumab Fab was measured by SDS-PAGE...

  15. Assessment of DCE-MRI parameters for brain tumors through implementation of physiologically-based pharmacokinetic model approaches for Gd-DOTA.

    Science.gov (United States)

    Spanakis, Marios; Kontopodis, Eleftherios; Van Cauter, Sophie; Sakkalis, Vangelis; Marias, Kostas

    2016-10-01

    Dynamic-contrast enhanced magnetic resonance imaging (DCE-MRI) is used for detailed characterization of pathology of lesions sites, such as brain tumors, by quantitative analysis of tracer's data through the use of pharmacokinetic (PK) models. A key component for PK models in DCE-MRI is the estimation of the concentration-time profile of the tracer in a nearby vessel, referred as Arterial Input Function (AIF). The aim of this work was to assess through full body physiologically-based pharmacokinetic (PBPK) model approaches the PK profile of gadoteric acid (Gd-DOTA) and explore potential application for parameter estimation in DCE-MRI based on PBPK-derived AIFs. The PBPK simulations were generated through Simcyp(®) platform and the predicted PK parameters for Gd-DOTA were compared with available clinical data regarding healthy volunteers and renal impairment patients. The assessment of DCE-MRI parameters was implemented by utilizing similar virtual profiles based on gender, age and weight to clinical profiles of patients diagnosed with glioblastoma multiforme. The PBPK-derived AIFs were then used to compute DCE-MRI parameters through the Extended Tofts Model and compared with the corresponding ones derived from image-based AIF computation. The comparison involved: (i) image measured AIF of patients vs AIF of in silico profile, and, (ii) population average AIF vs in silico mean AIFs. The results indicate that PBPK-derived AIFs allowed the estimation of comparable imaging biomarkers with those calculated from typical DCE-MRI image analysis. The incorporation of PBPK models and potential utilization of in silico profiles to real patient data, can provide new perspectives in DCE-MRI parameter estimation and data analysis. PMID:27647272

  16. Interaction Mechanism of Anthracene with Benzoic Acid and Its Derivatives

    Institute of Scientific and Technical Information of China (English)

    HE Ying-Ying; WANG Xiao-Chang; FAN Xiao-Yuan; ZHAO Bo; JIN Peng-Kang

    2008-01-01

    Interaction mechanism of anthracene, one of the typical polycyclic aromatic hydrocarbons, with benzoic acid and its hydroxyl-substituted derivatives, o-hydroxylbenzoic acid and p-hydroxylbenzoic acid, were studied using FFIR, UV and fluorescence spectra. The experiments confirmed that there was a specific and oriented interaction between anthracene and the aromatic carboxylic acids, and the bonding mode depended on both the chemical struc- ture of reactants and acidity of solution. The π-H hydrogen bond played a main role in the interaction between an-thracene and the aromatic carboxylic proton of benzoic acid or o-hydroxylbenzoic acid when pH≤pK, and the π-π electron donor-acceptor (EDA) interaction increasingly became the main binding mode when pH>pK. The de-crease of interaction intensity of benzoic acid was observed by introducing hydroxyl at its ortho position. The spe-cial D-π-A structure of p-hydroxylbenzoic acid made it easy to form the planar multi-molecule congeries that could interact with anthracene, so the interaction between anthracene and p-hydroxylbenzoic acid always followed the π-π EDA model no matter the solution acidity. For p-hydroxylbenzoic acid, the π-π interaction mode remained un-changed when pH increased from 2.0 to 10.0, and the binding intensity was higher than that between benzoic acid and anthracene because of the formation of the multi-molecule congeries.

  17. Direct amidation of amino acid derivatives catalyzed by arylboronic acids : applications in dipeptide synthesis.

    OpenAIRE

    Liu, S.; Yang, Y.; Liu, X.; Ferdousi, F. K.; Batsanov, A.S.; Whiting, A

    2013-01-01

    The direct amidation of amino acid derivatives catalyzed by arylboronic acids has been examined. The reaction was generally slow relative to simple amine-carboxylic acid combinations though proceeded at 65–68 °C generally avoiding racemization. 3,4,5-Trifluorophenylboronic and o-nitrophenylboronic acids were found to be the best catalysts, though for slower dipeptide formations, high catalyst loadings were required and an interesting synergistic catalytic effect between two arylboronic acids ...

  18. Synthesis and mesomorphic behaviour of lithocholic acid derivatives

    Indian Academy of Sciences (India)

    V A E Shaikh; N N Maldar; S V Lonikar

    2003-08-01

    A series of liquid crystalline derivatives of lithocholic acid were prepared using simple chemical reactions involving the terminal functional group—hydroxyl at C-3 and/or carboxyl at C-24. Thus methyl -3-(3-carboxy propionyl) lithocholate (I), 3-(3-carboxy propionyl) lithocholic acid (II), 3-acetyl lithocholic acid (III), 3-propionyl lithocholic acid (IV), 3-benzoyl lithocholic acid (V), 3-(4-nitrobenzoyl) lithocholic acid (VI), 3-cinnamoyl lithocholic acid (VII), methyl-3-(4-nitrobenzoyl) lithocholate (VIII) and 1,4-bis [cholan-24-methoxy carbonyl-3-oxycarbonyl] butane (IX) were prepared in good yields and characterized by IR, NMR and polarizing optical microscopy. Compounds (I) and (IX) exhibited monotropic behaviour while the others were enantiotropic. Some of the compounds also showed a high tendency of super cooling. Compounds (V), (VI) and (IX) formed cholesteric phase while the remaining compounds displayed smectic phase.

  19. Oleanolic acid and related derivatives as medicinally important compounds.

    Science.gov (United States)

    Sultana, Nighat; Ata, Athar

    2008-12-01

    Oleanolic acid has been isolated from chloroform extract of Olea ferruginea Royle after removal of organic bases and free acids. The literature survey revealed it to be biologically very important. In this review the biological significance of oleanolic acid and its derivatives has been discussed. The aim of this review is to update current knowledge on oleanolic acid and its natural and semisynthetic analogs, focussing on its cytotoxic, antitumer, antioxidant, anti-inflamatory, anti-HIV, acetyl cholinesterase, alpha-glucosidase, antimicrobial, hepatoprotective, anti-inflammatory, antipruritic, spasmolytic activity, anti-angiogenic, antiallergic, antiviral and immunomodulatory activities. We present in this review, for the first time, a compilation of the most relevant scientific papers and technical reports of the chemical, pre-clinical and clinical research on the properties of oleanolic acid and its derivatives.

  20. Oleanolic acid and related derivatives as medicinally important compounds.

    Science.gov (United States)

    Sultana, Nighat; Ata, Athar

    2008-12-01

    Oleanolic acid has been isolated from chloroform extract of Olea ferruginea Royle after removal of organic bases and free acids. The literature survey revealed it to be biologically very important. In this review the biological significance of oleanolic acid and its derivatives has been discussed. The aim of this review is to update current knowledge on oleanolic acid and its natural and semisynthetic analogs, focussing on its cytotoxic, antitumer, antioxidant, anti-inflamatory, anti-HIV, acetyl cholinesterase, alpha-glucosidase, antimicrobial, hepatoprotective, anti-inflammatory, antipruritic, spasmolytic activity, anti-angiogenic, antiallergic, antiviral and immunomodulatory activities. We present in this review, for the first time, a compilation of the most relevant scientific papers and technical reports of the chemical, pre-clinical and clinical research on the properties of oleanolic acid and its derivatives. PMID:18618318

  1. Functionalization of a Triazine Dendrimer Presenting Four Maleimides on the Periphery and a DOTA Group at the Core.

    Science.gov (United States)

    Lee, Changsuk; Ji, Kun; Simanek, Eric E

    2016-01-01

    A readily and rapidly accessible triazine dendrimer was manipulated in four steps with 23% overall yield to give a construct displaying four maleimide groups and DOTA. The maleimide groups of the dendrimer are sensitive to hydrolysis under basic conditions. The addition of up to four molecules of water can be observed via mass spectrometry and HPLC. The evolution in the alkene region of the ¹H-NMR--the transformation of the maleimide singlet to the appearance of two doublets--is consistent with imide hydrolysis and not the Michael addition. The hydrolysis events that proceeded over hours are sufficiently slower than the desired thiol addition reactions that occur in minutes. The addition of thiols to maleimides can be accomplished in a variety of solvents. The thiols examined derived from cysteine and include the protected amino acid, a protected dipeptide, and native oligopeptides containing either 9 or 18 amino acids. The addition reactions were monitored with HPLC and mass spectrometry in most cases. Complete substitution was observed for small molecule reactants. The model peptides containing nine or eighteen amino acids provided a mixture of products averaging between 3 and 4 substitutions/dendrimer. The functionalization of the chelate group with gadolinium was also accomplished easily. PMID:26978338

  2. Development of [64Cu]-DOTA-anti-CD20 for targeted therapy

    International Nuclear Information System (INIS)

    Copper-64 was produced as a by-product of 55Co via 64Ni(p,n)64Cu by 15 MeV proton bombardment of natNi resulting in a thick target yield of 5.31 MBq/μAh (143.5 μCi/μAh) and a radiochemical separation yield of 95% (radionuclide purity >97% after 25 hours of bombardment). Rituximab was successively labeled with [64Cu]-CuCl2. N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 deg C using DOTA and N-hydroxy succinimide (NHS) in CH2Cl2 followed by the addition of 1 ml of a Rituximab pharmaceutical solution. Radiolabeling was performed at 37 deg C in 3 hours. Radio thin-layer chromatography showed an overall radiochemical purity of 90-95% at optimized conditions (specific activity=30 GBq/mg, labeling efficacy; 82%) using various chromatography systems. The final isotonic 64Cu- DOTA-Rituximab complex was passed through a 0.22 μm filter and checked by gel electrophoresis for radiolysis control. Stability of the final product was checked in the formulation and in presence of human serum at 37 deg C. (author)

  3. Conformational Interconversions of Amino Acid Derivatives.

    Science.gov (United States)

    Kaminský, Jakub; Jensen, Frank

    2016-02-01

    Exhaustive conformational interconversions including transition structure analyses of N-acetyl-l-glycine-N-methylamide as well as its alanine, serine, and cysteine analogues have been investigated at the MP2/6-31G** level, yielding a total of 142 transition states. Improved estimates of relative energies were obtained by separately extrapolating the Hartree-Fock and MP2 energies to the basis set limit and adding the difference between CCSD(T) and MP2 results with the cc-pVDZ basis set to the extrapolated MP2 results. The performance of eight empirical force fields (AMBER94, AMBER14SB, MM2, MM3, MMFFs, CHARMM22_CMAP, OPLS_2005, and AMOEBAPRO13) in reproducing ab initio energies of transition states was tested. Our results indicate that commonly used class I force fields employing a fixed partial charge model for the electrostatic interaction provide mean errors in the ∼10 kJ/mol range for energies of conformational transition states for amino acid conformers. Modern reparametrized versions, such as CHARMM22_CMAP, and polarizable force fields, such as AMOEBAPRO13, have slightly lower mean errors, but maximal errors are still in the 35 kJ/mol range. There are differences between the force fields in their ability for reproducing conformational transitions classified according to backbone/side-chain or regions in the Ramachandran angles, but the data set is likely too small to draw any general conclusions. Errors in conformational interconversion barriers by ∼10 kJ/mol suggest that the commonly used force field may bias certain types of transitions by several orders of magnitude in rate and thus lead to incorrect dynamics in simulations. It is therefore suggested that information for conformational transition states should be included in parametrizations of new force fields. PMID:26691979

  4. TmDOTA-tetraglycinate encapsulated liposomes as pH-sensitive LipoCEST agents.

    Directory of Open Access Journals (Sweden)

    Ana Christina L Opina

    Full Text Available Lanthanide DOTA-tetraglycinate (LnDOTA-(gly₄⁻ complexes contain four magnetically equivalent amide protons that exchange with protons of bulk water. The rate of this base catalyzed exchange process has been measured using chemical exchange saturation transfer (CEST NMR techniques as a function of solution pH for various paramagnetic LnDOTA-(gly₄⁻ complexes to evaluate the effects of lanthanide ion size on this process. Complexes with Tb(III, Dy(III, Tm(III and Yb(III were chosen because these ions induce large hyperfine shifts in all ligand protons, including the exchanging amide protons. The magnitude of the amide proton CEST exchange signal differed for the four paramagnetic complexes in order, Yb>Tm>Tb>Dy. Although the Dy(III complex showed the largest hyperfine shift as expected, the combination of favorable chemical shift and amide proton CEST linewidth in the Tm(III complex was deemed most favorable for future in vivo applications where tissue magnetization effects can interfere. TmDOTA-(gly₄⁻ at various concentrations was encapsulated in the core interior of liposomes to yield lipoCEST particles for molecular imaging. The resulting nanoparticles showed less than 1% leakage of the agent from the interior over a range of temperatures and pH. The pH versus amide proton CEST curves differed for the free versus encapsulated agents over the acidic pH regions, consistent with a lower proton permeability across the liposomal bilayer for the encapsulated agent. Nevertheless, the resulting lipoCEST nanoparticles amplify the CEST sensitivity by a factor of ∼10⁴ compared to the free, un-encapsulated agent. Such pH sensitive nano-probes could prove useful for pH mapping of liposomes targeted to tumors.

  5. Antibacterial and Antioxidant Activities of Ursolic Acid and Derivatives

    Directory of Open Access Journals (Sweden)

    Patrícia G.G. do Nascimento

    2014-01-01

    Full Text Available Ursolic acid, an important bioactive compound, was isolated from ethanol extract of aerial parts of Sambucus australis. In order to develop bioactive ursolic acid derivatives, two semi-synthetic compounds were obtained through modification at C-3. The antibacterial activity of the ursolic acid and its derivatives was investigated. The microdilution method was used for determination of the minimal inhibitory concentration (MIC, against twelve bacterial strains. The influence of ursolic acid and its derivatives on the susceptibility of some bacterial pathogens to the aminoglycosides antibiotics neomycin, amikacin, kanamycin and gentamicin was evaluated. The most representative synergistic effect was observed by 3β-formyloxy-urs-12-en-28-oic acid at the concentration of 64 μg/mL in combination with kanamycin against Escherichia coli (27, a multidrug-resistant clinical isolate from sputum, with reduction of MIC value from 128 μg/mL to 8 μg/mL. Ursolic acid and its derivatives were examined for their radical scavenger activity using the DPPH assay, and showed significant activity.

  6. SYNTHESIS AND PHARMACOLOGICAL SCREENING OF NSUBSTITUTED ANTHRANILIC ACID DERIVATIVES

    Directory of Open Access Journals (Sweden)

    Dileep Tiwari

    2011-06-01

    Full Text Available In the present work eight newly synthesized structurally diverse anthranilic acid derivatives were evaluated for their anti-inflammatory activity against carrageenan induced oedema in albino rats. All the anthranilic acid derivatives were compared for their percentage inhibition of the oedema using control drug phenylbutazone. The desired anthranilic acid derivatives 5-bromo-2-{[5-{[(2E-3-(2- substitutedphenylprop-2-enoyl]amino}-1,3,4,-oxadiazol-2- yl methyl]amino}benzoic acid (compounds 1-4 were synthesized by condensation of 5-bromo-N - (2'-amino acetyl -1',3',4'-oxadiazol-5'-ylmethyl anthranilic acid and substituted aromatic aldehydes, respectively, and the compounds 5-bromo-N – [2'-amino [1"-acetyl-5''- (substitutedaryl-2'-pyrazolin-3"-yl]-1'3'4'-oxadiazol-5'- ylmethyl anthranilic acid (compounds 5-8 were synthesized by the condensation of compounds (1-4 with the hydrazine hydrate in the presence of few drops of glacial acetic acid. Compound 5 was found to be a potent member of this series which showed 51.05% antiinflammatory activity with ED50 of 51.05 mg/kg while phenylbutazone exhibited 47.23% anti-inflammatory activity at the same dose. The structures of the newly synthesized compounds have been established on the basis of spectral (FTIR and 1H-NMR data and elemental analysis.

  7. Effect of amino acids and amino acid derivatives on crystallization of hemoglobin and ribonuclease A

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Len, E-mail: len@ksc.kwansei.ac.jp; Kobayashi, Toyoaki [School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337 (Japan); Shiraki, Kentaro [Institute of Applied Physics, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573 (Japan); Yamaguchi, Hiroshi [School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337 (Japan)

    2008-05-01

    The effect of the addition of amino acids and amino acid derivatives on the crystallization of hemoglobin and ribonuclease A has been evaluated. The results showed that certain types of additives expand the concentration conditions in which crystals are formed. Determination of the appropriate conditions for protein crystallization remains a highly empirical process. Preventing protein aggregation is necessary for the formation of single crystals under aggregation-prone solution conditions. Because many amino acids and amino acid derivatives offer a unique combination of solubility and stabilizing properties, they open new avenues into the field of protein aggregation research. The use of amino acids and amino acid derivatives can potentially influence processes such as heat treatment and refolding reactions. The effect of the addition of several amino acids, such as lysine, and several amino acid derivatives, such as glycine ethyl ester and glycine amide, on the crystallization of equine hemoglobin and bovine pancreatic ribonuclease A has been examined. The addition of these amino acids and amino acid derivatives expanded the range of precipitant concentration in which crystals formed without aggregation. The addition of such additives appears to promote the crystallization of proteins.

  8. Optimization of Time-Resolved Fluorescence Assay for Detection of Eu-DOTA-labeled Ligand-Receptor Interactions

    OpenAIRE

    De Silva, Channa R.; Vagner, Josef; Lynch, Ronald; Gillies, Robert J.; Hruby, Victor J.

    2009-01-01

    Lanthanide-based luminescent ligand binding assays are superior to traditional radiolabel assays due to improved sensitivity and affordability in high throughput screening while eliminating the use of radioactivity. Despite significant progress using lanthanide(III)-coordinated chelators such as DTPA derivatives, dissociation-enhanced lanthanide fluoroimmunoassays (DELFIA) have not yet been successfully used with more stable chelators, e.g. DOTA derivatives, due to the incomplete release of l...

  9. Tumor targeting using 67Ga-DOTA-Bz-folate - investigations of methods to improve the tissue distribution of radiofolates

    International Nuclear Information System (INIS)

    Introduction: Use of folic acid radioconjugates for folate receptor (FR) targeting is a promising strategy for imaging purposes as well as for potential therapy of cancer and inflammatory diseases due to the frequent FR overexpression found on cancer cells and activated macrophages. Herein, we report on preclinical results using a novel DOTA-Bz-EDA-folate conjugate radiolabeled with [67Ga]-gallium. Methods: DOTA-Bz-EDA-folate was prepared by conjugation of ethylenediamine-(γ)-folate with 2-(p-isothiocyanobenzyl)-DOTA. Radiolabeling was carried out with 67GaCl3 according to standard procedures. Biodistribution studies of the tracer were performed in mice bearing FR-positive KB tumor xenografts. The effects on radiofolate biodistribution with coadministered renal uptake-blocking amino acids, diuretic agents, antifolates as well as different routes of administration were likewise investigated. Supportive imaging studies were performed using a small-animal single photon emission computed tomography (SPECT)/CT scanner. Results: 67Ga-DOTA-Bz-EDA-folate showed a high and specific accumulation in tumors (6.30%±0.75% ID/g, 1 h pi and 6.08%±0.89% ID/g, 4 h pi). Nonspecific radioactivity uptake in nontargeted tissues was negligible, but significant accumulation was found in FR-positive kidneys, which resulted in unfavorably low tumor-to-kidney ratios (67Ga-radiofolate and the favorable reduction in kidney uptake (with improved imaging quality) resulting from pemetrexed administration. Conclusion: Conventional methods to reduce kidney uptake of radiofolates fail. However, the novel 67Ga-radiolabeled DOTA-Bz-EDA-folate can effectively be used to image FR-positive cancer and potentially inflammatory diseases. Due to its rapid blood clearance properties, this tracer is also a promising candidate for positron emission tomography imaging if radiolabeled with the short-lived [68Ga]-gallium radionuclide.

  10. Preparation & in vitro evaluation of 90 Y-DOTA-rituximab

    Directory of Open Access Journals (Sweden)

    Mythili Kameswaran

    2016-01-01

    Full Text Available Background & objectives: Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin′s lymphoma (NHL. Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA to rituximab, its radiolabelling with [90] Y and in vitro and in vivo evaluation to determine its potential as a radioimmunotherapeutic agent. Methods: Rituximab was conjugated with p-SCN-Bn-DOTA at 1:1 antibody: DOTA molar ratio. The number of DOTA molecules linked to one molecule of rituximab was determined by radioassay and spectroscopic assay. Radiolabelling of rituximab with 90 Y was carried out and its in vitro stability was evaluated. In vitro cell binding studies were carried out in Raji cells expressing CD20 antigen. Biodistribution studies were carried out in normal Swiss mice. Results: Using both radioassay and spectroscopic method, it was determined that about five molecules of DOTA were linked to rituximab. Radiolabelling of the rituximab conjugate with [90] Y and subsequent purification on PD-10 column gave a product with radiochemical purity (RCP > 98 per cent which was retained at > 90 per cent up to 72 h when stored at 37°C. In vitro cell binding experiments of 90 Y-DOTA-rituximab with Raji cells exhibited specific binding of 20.7 ± 0.1 per cent with [90] Y-DOTA-rituximab which reduced to 15.5 ± 0.2 per cent when incubated with cold rituximab. The equilibrium constant K d for 90 Y-DOTA-Rituximab was determined to be 3.38 nM. Radiolabelled antibody showed clearance via hepatobiliary and renal routes and activity in tibia was found to be quite low indicating in vivo stability of [90] Y-DOTA-rituximab. Interpretation & conclusions: p-SCN-Bn-DOTA was conjugated with rituximab and radiolabelling with 90 Y was

  11. Comparison of 90Y/177Lu labeled DOTA-Bz-RGD tetramer and DOTA-RGD tetramer

    International Nuclear Information System (INIS)

    90Y/177Lu labeled DOTA-Bz-RGD tetramer and DOTA-RGD tetramer were prepared, and the effect of Bz-DOTA and DOTA on labeling conditions and in vitro stability of radiolabeled compounds was compared. The labeling conditions, including reaction pH, reaction temperature and reaction time, were investigated. ITLC and HPLC show that the labeling yields of four radiolabeled compounds are more than 95% under optimal conditions (pH=6.0, reacting at 100 degree C for 15-20 min); the four radiolabeled compounds show pretty good stability in saline and fetal bovine serum. Although introducing of Bz has no effect on labeling conditions and in vitro stability of radiolabeled compounds, it brings a little change on molecule polarity. HPLC analysis and lg P values reveal that introducing of Bz increases the lipophilicity of radiolabeled compounds. (authors)

  12. Comparison of [177Lu-DOTA0,Tyr3]octreotate and [177Lu-DOTA0,Tyr3]octreotide: which peptide is preferable for PRRT?

    International Nuclear Information System (INIS)

    Patients with somatostatin receptor subtype 2-positive metastasised neuroendocrine tumours can be treated with [177Lu-DOTA0,Tyr3]octreotate. Some use octreotide as the peptide for peptide receptor radionuclide therapy (PRRT). We compared in seven patients [177Lu-DOTA0,Tyr3]octreotide (177Lu-DOTATOC) and [177Lu-DOTA0,Tyr3]octreotate (177Lu-DOTATATE), to see which peptide should be preferred for PRRT with 177Lu. In the same patients, 3,700 MBq 177Lu-DOTATOC and 3,700 MBq 177Lu-DOTATATE was administered in separate therapy sessions. Amino acids were co-administered. Whole-body scanning was performed on days 1, 4 and 7 post therapy. Blood and urine samples were collected. We calculated residence times for tumours, spleen and kidneys. All patients had longer residence times in spleen, kidneys and tumours after use of 177Lu-DOTATATE (p=0.016 in each case). Comparing 177Lu-DOTATATE with 177Lu-DOTATOC, the mean residence time ratio was 2.1 for tumour, 1.5 for spleen and 1.4 for kidneys. Dose-limiting factors for PRRT are bone marrow and/or kidney dose. Although the residence time for kidneys was longer when using 177Lu-DOTATATE, the mean administered dose to tumours would still be advantageous by a factor of 1.5, assuming a fixed maximum kidney dose is reached. Plasma radioactivity after 177Lu-DOTATATE was comparable to that after 177Lu-DOTATOC. Urinary excretion of radioactivity was comparable during the first 6 h; thereafter there was a significant advantage for 177Lu-DOTATOC. 177Lu-DOTATATE had a longer tumour residence time than 177Lu-DOTATOC. Despite a longer residence time in kidneys after 177Lu-DOTATATE, tumour dose will always be higher. Therefore, we conclude that the better peptide for PRRT is octreotate. (orig.)

  13. Synthesis and Antiviral Activity of Hydrogenated Ferulic Acid Derivatives

    OpenAIRE

    Can Cui; Zhi-Peng Wang; Xiu-jiang Du; Li-Zhong Wang; Shu-Jing Yu; Xing-Hai Liu; Zheng-Ming Li; Wei-Guang Zhao

    2013-01-01

    A series of hydrogenated ferulic acid amide derivatives 4 were synthesized. The molecular structures of the synthesized compounds were analyzed by H1 NMR and HRMS. The biological activity study showed that some of them displayed excellent protection activity and curative activity against TMV at 500 μg/mL.

  14. Conformation of some carboxylic acids and their derivatives

    NARCIS (Netherlands)

    Kanters, J.A.; Kroon, Jan; Peerdeman, A.F.; Schoone, J.C.

    1967-01-01

    The conformation in the crystalline state of some aliphatic carboxylic acids and their derivatives has been analysed. This analysis, based upon the results of structure determinations by means of X-ray diffraction, seems to support the concept that the conformation of a molecule is governed chiefly

  15. SPECT/CT of lung nodules using 111In-DOTA-c(RGDfK) in a mouse lung carcinogenesis model

    International Nuclear Information System (INIS)

    Lung cancer is one of the leading causes of cancer-related deaths worldwide, including Japan. Although computed tomography (CT) can detect small lung lesions such as those appearing as ground glass opacity, it cannot differentiate between malignant and non-malignant lesions. Previously, we have shown that single photon emission computed tomography (SPECT) imaging using 111In-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-cyclo-(Arg-Gly-Asp-D-Phe-Lys) (DOTA-c(RGDfK)), an imaging probe of αvβ3 integrin, is useful for the early detection of pancreatic cancer in a hamster pancreatic carcinogenesis model. In this study, we aimed to assess the usefulness of SPECT/CT with 111In-DOTA-c(RGDfK) for the evaluation of the malignancy of lung cancer. Lung tumors were induced by a single intraperitoneal injection (250 mg/kg) of urethane in male A/J mice. Twenty-six weeks after the urethane treatment, SPECT was performed an hour after injection of 111In-DOTA-c(RGDfK). Following this, the radioactivity ratios of tumor to normal lung tissue were measured by autoradiography (ARG) in the excised lung samples. We also examined the expression of αvβ3 integrin in mouse and human lung samples. Urethane treatment induced 5 hyperplasias, 41 adenomas and 12 adenocarcinomas in the lungs of 8 A/J mice. SPECT with 111In-DOTA-c(RGDfK) could clearly visualize lung nodules, though we failed to detect small lung nodules like adenoma and hyperplasias (adenocarcinoma: 66.7%, adenoma: 33.6%, hyperplasia: 0.0%). ARG analysis revealed significant uptake of 111In-DOTA-c(RGDfK) in all the lesions. Moreover, tumor to normal lung tissue ratios increased along with the progression of carcinogenesis. Histopathological examination using human lung tissue samples revealed clear up-regulation of αvβ3 integrin in well-differentiated adenocarcinoma (Noguchi type B and C) rather than atypical adenomatous hyperplasia. Although there are some limitations in evaluating the malignancy of small lung

  16. radiolabeling of DOTA-substance P with 177Lu and biodistribution of 177Lu-DOTA-substance P

    International Nuclear Information System (INIS)

    The aim of this project is to evaluate the biodistribution of 177Lu-DOTA-SP in normal mice and in PANC-1 tumor bearing nude mice and to pave the way for its potentially medical application. In this study, 177Lu-DOTA-SP was successfully prepared with labeling yield of greater than 90% at optimized conditions and more than 98% of radiochemical purity after C18 Sep-Pak purification. 177Lu-DOTA-SP showed good stability in saline and in 5% serum while it decomposed slowly in 10% serum. Biodistribution studies in normal mice showed high uptake of 177Lu-DOTA-SP in the kidneys, indicating the excretion mainly by renal pathway. In addition, 177Lu-DOTA-SP was washed out from the blood quickly. Bio- distribution of 177Lu-DOTA-SP in PANC-1 tumor bearing mice showed higher uptake in pancreatic tumor than that in normal pancreas, indicating the presence of NK-1 receptors in PANC-1 pancreatic tumor. However, from SPECT image, no radioactivity accumulation was observed in PANC-1 tumor. Further evaluation is needed to confirm its potential application for radiotherapy of pancreatic cancers. (authors)

  17. Amino acid decarboxylations produced by lipid-derived reactive carbonyls in amino acid mixtures.

    Science.gov (United States)

    Hidalgo, Francisco J; León, M Mercedes; Zamora, Rosario

    2016-10-15

    The formation of 2-phenylethylamine and phenylacetaldehyde in mixtures of phenylalanine, a lipid oxidation product, and a second amino acid was studied to determine the role of the second amino acid in the degradation of phenylalanine produced by lipid-derived reactive carbonyls. The presence of the second amino acid usually increased the formation of the amine and reduced the formation of the Strecker aldehyde. The reasons for this behaviour seem to be related to the α-amino group and the other functional groups (mainly amino or similar groups) present in the side-chain of the amino acid. These groups are suggested to modify the lipid-derived reactive carbonyl but not the reaction mechanism because the Ea of formation of both 2-phenylethylamine and phenylacetaldehyde remained unchanged in all studied systems. All these results suggest that the amine/aldehyde ratio obtained by amino acid degradation can be modified by adding free amino acids during food formulation. PMID:27173560

  18. Caldensinic acid, a benzoic acid derivative and others compounds from Piper carniconnectivum

    Energy Technology Data Exchange (ETDEWEB)

    Alves, Harley da Silva; Souza, Maria de Fatima Vanderlei de; Chaves, Maria Celia de Oliveira, E-mail: cchaves@ltf.ufpb.b [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Lab. de Tecnologia Farmaceutica

    2010-07-01

    A benzoic acid derivative - caldensinic acid, E-phythyl hexadecanoate, {beta}-sitosterol and stigmasterol mixture and phaeophytin a were isolated from the aerial parts of Piper carniconnectivum. The structures of these compounds were established unambiguously by IR, MS, 1D and 2D NMR analysis. (author)

  19. Copper(I) mediated cross-coupling of amino acid derived organozinc reagents with acid chlorides

    DEFF Research Database (Denmark)

    Hjelmgaard, Thomas; Tanner, David Ackland

    2006-01-01

    This paper describes the development of a straightforward experimental protocol for copper-mediated cross-coupling of amino acid derived beta-amido-alkylzinc iodides 1 and 3 with a range of acid chlorides. The present method uses CuCN center dot 2LiCl as the copper source and for organozinc reagent...

  20. 64Cu-DOTA-trastuzumab PET imaging and HER2 specificity of brain metastases in HER2-positive breast cancer patients

    OpenAIRE

    Kurihara, Hiroaki; Hamada, Akinobu; Yoshida, Masayuki; Shimma, Schuichi; Hashimoto, Jun; YONEMORI, KAN; Tani, Hitomi; Miyakita, Yasuji; Kanayama, Yousuke; Wada, Yasuhiro; Kodaira, Makoto; Yunokawa, Mayu; Yamamoto, Harukaze; Shimizu, Chikako; Takahashi, Kazuhiro

    2015-01-01

    Background The purpose of this study was to determine whether brain metastases from HER2-positive breast cancer could be detected noninvasively using positron emission tomography (PET) with 64Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-trastuzumab. Methods PET was performed on five patients with brain metastases from HER2-positive breast cancer, at 24 or 48 h after the injection of approximately 130 MBq of the probe 64Cu-DOTA-trastuzumab. Radioactivity in metastatic bra...

  1. Comparison and systematic optimization of synthetic protocols for DOTA-hydrazide generation

    NARCIS (Netherlands)

    Fuge, F.; Weiler, M.; Gaetjens, J.; Lammers, T.G.G.M.

    2013-01-01

    DOTA-based organometallic complexes are extensively used in functional and molecular imaging studies, as well as in radioimmunotherapy. DOTA forms thermodynamically stable and kinetically inert complexes with various different diagnostic and therapeutic metals, such as gadolinium, gallium, yttrium a

  2. 68Ga- and 111In-labelled DOTA-RGD peptides for imaging of αvβ3 integrin expression

    International Nuclear Information System (INIS)

    αvβ3 integrins are important cell adhesion receptors involved in angiogenic processes. Recently, we demonstrated using [18F]Galacto-RGD that monitoring of αvβ3 expression is feasible. Here, we introduce 68Ga- and 111In-labelled derivatives and compare them with [18F]Galacto-RGD. For radiolabelling, cyclo(RGDfK(DOTA)) was synthesised using SPPS. For in vitro characterisation determination of partition coefficients, protein binding, metabolic stability, αvβ3 affinity and cell uptake and for in vivo characterization, biodistribution studies and micro positron emission tomography (PET) imaging were carried out. For in vivo and in vitro studies, human melanoma M21 (αvβ3 positive) and M21-L (αvβ3 negative) cells were used. Both tracers can be synthesised straightforward. The compounds showed hydrophilic properties and high metabolic stability. Up to 23% protein-bound activity for [68Ga]DOTA-RGD and only up to 1.4% for [111In]DOTA-RGD was found. Cell uptake studies indicate receptor-specific accumulation. This is confirmed by the biodistribution data. One hour p.i. accumulation in αvβ3-positive tumours was 2.9 ± 0.3%ID/g and in αvβ3-negative tumours 0.8 ± 0.1%ID/g for [68Ga]DOTA-RGD ([111In]DOTA-RGD: 1.9 ± 0.3%ID/g and 0.5 ± 0.2%ID/g; [18F]Galacto-RGD: 1.6 ± 0.2%ID/g and 0.4 ± 0.1%ID/g). Thus, tumour uptake ratios were comparable. Due to approx. 3-fold higher blood pool activities for [68Ga]DOTA-RGD, tumour/blood ratios were higher for [111In]DOTA-RGD and [18F]Galacto-RGD. However, microPET studies demonstrated that visualisation of αvβ3-positive tumours using [68Ga]DOTA-RGD is possible. Our data indicate that [68Ga]DOTA-RGD allows monitoring of αvβ3 expression. Especially, the much easier radiosynthesis compared to [18F]Galacto-RGD would make it an attractive alternative. However, due to higher blood pool activity, [18F]Galacto-RGD remains superior for imaging αvβ3 expression. Introduction of alternative chelator systems may overcome the

  3. Biological Activities of Oleanolic Acid Derivatives from Calendula officinalis Seeds.

    Science.gov (United States)

    Zaki, Ahmed; Ashour, Ahmed; Mira, Amira; Kishikawa, Asuka; Nakagawa, Toshinori; Zhu, Qinchang; Shimizu, Kuniyoshi

    2016-05-01

    Phytochemical examination of butanol fraction of Calendula officinalis seeds led to the isolation of two compounds identified as 28-O-β-D-glucopyranosyl-oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS1) and oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS2). Biological evaluation was carried out for these two compounds such as melanin biosynthesis inhibitory, hyaluronic acid production activities, anti obesity using lipase inhibition and adipocyte differentiation as well as evaluation of the protective effect against hydrogen peroxide induced neurotoxicity in neuro-2A cells. The results showed that, compound CS2 has a melanin biosynthesis stimulatory activity; however, compound CS1 has a potent stimulatory effect for the production of hyaluronic acid on normal human dermal fibroblast from adult (NHDF-Ad). Both compounds did not show any inhibitory effect on both lipase and adipocyte differentiation. Compound CS2 could protect neuro-2A cells and increased cell viability against H2 O2 . These activities (melanin biosynthesis stimulatory and protective effect against H2 O2 of CS2 and hyaluronic acid productive activities of these triterpene derivatives) have been reported for the first time. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26887328

  4. Comparison of 111In-DOTA-DPhe1-Tyr3-octreotide and 111In-DOTA-lanreotide scintigraphy and dosimetry in patients with neuroendocrine tumours

    International Nuclear Information System (INIS)

    Somatostatin receptor scintigraphy with 111In-DOTA-DPhe1-Tyr3-octreotide (111In-DOTA-TOC) and 111In-DOTA-lanreotide (111In-DOTA-LAN) has been used for staging of neuroendocrine tumours (NETs). However, the comparative diagnostic value of these radioligands on a lesion basis has not yet been established. The aim of this study was to compare the diagnostic capacity of 111In-DOTA-TOC and 111In-DOTA-LAN scintigraphy in patients with NETs, evaluating whether significant differences exist in lesion imaging with these radioligands. Furthermore, dosimetric data were compared. Forty-five patients with NETs were investigated with 111In-DOTA-TOC and 111In-DOTA-LAN scintigraphy. Scintigraphic results were compared with those of conventional imaging and/or surgery in each patient, and also 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in 20 patients. 111In-DOTA-TOC and 111In-DOTA-LAN scintigraphy were true positive in 42/45 (93%) and 39/45 (87%) patients, and imaged 74/91 (81%) and 73/91 (80%) tumour lesions, respectively. 111In-DOTA-TOC and 111In-DOTA-LAN detected liver metastases in 21 and 14 patients, mediastinal metastases in seven and 11 patients, and bone metastases in two and seven patients, respectively. These radioligands revealed lesions not seen by conventional imaging in seven and eight patients, respectively, or by 18F-FDG-PET in eight and seven patients, respectively. The estimated tumour absorbed doses for 90Y-DOTA-TOC were higher than those for 90Y-DOTA-LAN in 14 patients, whereas the opposite was true in 12 patients. Both 111In-DOTA-TOC and 111In-DOTA-LAN are suitable for imaging tumour lesions in patients with NETs and can detect lesions that may not be seen by conventional imaging and 18F-FDG-PET. Compared with 111In-DOTA-LAN, 111In-DOTA-TOC has a superior diagnostic capacity for liver metastases, but a lower diagnostic capacity for metastatic lesions in mediastinum and bone. (orig.)

  5. Effect of DOTA Position on Melanoma Targeting and Pharmacokinetic Properties of 111In-labeled Lactam Bridge-Cyclized Alpha-Melanocyte Stimulating Hormone Peptide

    OpenAIRE

    Guo, Haixun; Yang,Jianquan; Gallazzi, Fabio; Prossnitz, Eric R.; Sklar, Larry A.; Miao, Yubin

    2009-01-01

    The purpose of this study was to examine the effect of DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) position on melanoma targeting and pharmacokinetics of radiolabeled lactam bridge-cyclized alpha-melanocyte stimulating hormone (α-MSH) peptide.

  6. Anacardic acid derivatives from Brazilian propolis and their antibacterial activity

    Energy Technology Data Exchange (ETDEWEB)

    Silva, M.S.S.; Lima, S.G. de; Lopes, J.A.D.; Chaves, M.H.; Cito, A.M.G.L. [Universidade Federal do Piaui (UFPI), Teresina, PI (Brazil). Dept. de Quimica]. E-mail: gracito@ufpi.br; Oliveira, E.H. [Universidade Federal do Piaui (UFPI), Teresina, PI (Brazil). Dept. de Microbiologia e Parasitologia; Reis, F.A.M. [Universidade Estadual de Campinas (UNICAMP), Campinas, SP (Brazil). Inst. de Quimica

    2008-07-01

    Propolis is a sticky, gummy, resinous substance collected by honeybees (Apis mellifera L.) from various plant sources, which has excellent medicinal properties. This paper describes the isolation and identification of triterpenoids and anacardic acid derivatives from Brazilian propolis and their antibacterial activity. Their structures were elucidated by {sup 1}H and {sup 13}C NMR, including uni- and bidimensional techniques; in addition, comparisons were made with data from academic literature. These compounds were identified as: cardanols (1a + 1b), cardols (2a + 2b), mono ene anacardic acid (3), alpha-amirine (4), beta-amirine (5), cycloartenol (6), 24-methylene-cycloartenol (7) and lupeol (8). The determination of the position of the double bond after a reaction with Dimethyl disulfide (DMDS) is described for the phenol derivatives. The ethanolic extract was tested in vitro for antimicrobial activity by using the disc diffusion method and it showed significant results against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Shigella spp. (author)

  7. [Cardioprotective properties of new glutamic acid derivative under stress conditions].

    Science.gov (United States)

    Perfilova, V N; Sadikova, N V; Berestovitskaia, V M; Vasil'eva, O S

    2014-01-01

    The effect of new glutamic acid derivative on the cardiac ino- and chronotropic functions has been studied in experiments on rats exposed to 24-hour immobilization-and-pain stress. It is established that glutamic acid derivative RGPU-238 (glufimet) at a dose of 28.7 mg/kg increases the increment of myocardial contractility and relaxation rates and left ventricular pressure in stress-tested animals by 13 1,1, 72.4, and 118.6%, respectively, as compared to the control group during the test for adrenoreactivity. Compound RGPU-238 increases the increment of the maximum intensity of myocardium functioning by 196.5 % at 30 sec of isometric workload as compared to the control group. The cardioprotective effect of compound RGPU-238 is 1.5 - 2 times higher than that of the reference drug phenibut. PMID:25365864

  8. Preparation and Biological Study of 68Ga-DOTA-alendronate

    Science.gov (United States)

    Fakhari, Ashraf; Jalilian, Amir R.; Johari-Daha, Fariba; Shafiee-Ardestani, Mehdi; Khalaj, Ali

    2016-01-01

    Objective(s): In line with previous research on the development of conjugated bisphosphonate ligands as new bone-avid agents, in this study, DOTA-conjugated alendronate (DOTA-ALN) was synthesized and evaluated after labeling with gallium-68 (68Ga). Methods: DOTA-ALN was synthesized and characterized, followed by 68Ga-DOTA-ALN preparation, using DOTA-ALN and 68GaCl3 (pH: 4-5) at 92-95° C for 10 min. Stability tests, hydroxyapatite assay, partition coefficient calculation, biodistribution studies, and imaging were performed on the developed agent in normal rats. Results: The complex was prepared with high radiochemical purity (>99% as depicted by radio thin-layer chromatography; specific activity: 310-320 GBq/mmol) after solid phase purification and was stabilized for up to 90 min with a log P value of -2.91. Maximum ligand binding (65%) was observed in the presence of 50 mg of hydroxyapatite; a major portion of the activity was excreted through the kidneys. With the exception of excretory organs, gastrointestinal tract organs, including the liver, intestine, and colon, showed significant uptake; however, the bone uptake was low (<1%) at 30 min after the injection. The data were also confirmed by sequential imaging at 30-90 min following the intravenous injection. Conclusion: The high solubility and anionic properties of the complex led to major renal excretion and low hydroxyapatite uptake; therefore, the complex failed to demonstrate bone imaging behaviors. PMID:27408898

  9. Preparation and biological studies of 68Ga-DOTA-alendronate

    Directory of Open Access Journals (Sweden)

    Ashraf Fakhari

    2016-07-01

    Full Text Available Objective(s: In line with previous research on the development of conjugated bisphosphonate ligands as new bone-avid agents, in this study, DOTA conjugated alendronate (DOTA-ALN was synthesized and evaluated after labeling with gallium-68 (68Ga.Methods: DOTA-ALN was synthesized and characterized, followed by 68Ga-DOTA-ALN preparation, using DOTA-ALN and 68GaCl3 (pH: 4-5 at 92-95°C for 10 min. Stability tests, hydroxyapatite assay, partition coefficient calculation,biodistribution studies, and imaging were performed on the developed agent in normal rats.Results: The complex was prepared with high radiochemical purity (>99% as depicted by radio thin-layer chromatography; specific activity: 310-320GBq/mmol after solid phase purification and was stabilized for up to 90 min with a logP value of -2.91. Maximum ligand binding (65% was observed in the presence of 50 mg of hydroxyapatite; a major portion of the activity was excreted through the kidneys. With the exception of excretory organs, gastrointestinal tract organs, including the liver, intestine, and colon, showed significant uptake; however, the bone uptake was low (

  10. Preparation and Biodistribution Evaluation in Mice of ~(177)Lu-DOTA-TOC

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The study of 177Lu labeled radiopharmaceuticals for cancer therapy is fast emerging as an important part of nuclear medicine. 177Lu-labelling of DOTA derivatized peptide DOTA-TOC (Tyr3-Octreotide) was carried out and biodistribution of 177Lu-DOTA-TOC in normal

  11. Ionic products of metal complexes with dithiocarbonic acid derivatives

    International Nuclear Information System (INIS)

    Ionic products of the complexes of certain sulfide-forming metal ions (In, Cd, Te, etc.) with alkyl derivates of dithiocarbonic acid have been defined. The possibility to use ionic products of alkyl xanthates for predicting the practicability of employing alkyl xanthates as analytic reagents in titrimetric methods of analysis, in extractional methods of separation and determination of elements, increase in the determination selectivity, is shown. 11 refs., 1 fig., 1 tab

  12. Somatostatin-based radiopeptide therapy with [{sup 177}Lu-DOTA]-TOC versus [{sup 90}Y-DOTA]-TOC in neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Romer, A.; Seiler, D.; Brunner, P.; Ng, Q.K.T.; Mueller-Brand, J. [University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); Marincek, N.; Walter, M.A. [University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); University Hospital Bern, Institute of Nuclear Medicine, Bern (Switzerland); Koller, M.T. [University Hospital Basel, Basel Institute for Clinical Epidemiology and Biostatistics, Basel (Switzerland); Maecke, H.R. [University Hospital Basel, Division of Radiochemistry, Basel (Switzerland); Rochlitz, C. [University Hospital Basel, Department of Oncology, Basel (Switzerland); Briel, M. [University Hospital Bern, Institute of Nuclear Medicine, Bern (Switzerland); University Hospital Basel, Basel Institute for Clinical Epidemiology and Biostatistics, Basel (Switzerland); McMaster University, Department of Clinical Epidemiology and Biostatistics, Hamilton (Canada); Schindler, C. [University of Basel, Swiss Tropical and Public Health Institute, Basel (Switzerland)

    2014-02-15

    Somatostatin-based radiopeptide treatment is generally performed using the β-emitting radionuclides {sup 90}Y or {sup 177}Lu. The present study aimed at comparing benefits and harms of both therapeutic approaches. In a comparative cohort study, patients with advanced neuroendocrine tumours underwent repeated cycles of [{sup 90}Y-DOTA]-TOC or [{sup 177}Lu-DOTA]-TOC until progression of disease or permanent adverse events. Multivariable Cox regression and competing risks regression were employed to examine predictors of survival and adverse events for both treatment groups. Overall, 910 patients underwent 1,804 cycles of [{sup 90}Y-DOTA]-TOC and 141 patients underwent 259 cycles of [{sup 177}Lu-DOTA]-TOC. The median survival after [{sup 177}Lu-DOTA]-TOC and after [{sup 90}Y-DOTA]-TOC was comparable (45.5 months versus 35.9 months, hazard ratio 0.91, 95 % confidence interval 0.63-1.30, p = 0.49). Subgroup analyses revealed a significantly longer survival for [{sup 177}Lu-DOTA]-TOC over [{sup 90}Y-DOTA]-TOC in patients with low tumour uptake, solitary lesions and extra-hepatic lesions. The rate of severe transient haematotoxicities was lower after [{sup 177}Lu-DOTA]-TOC treatment (1.4 vs 10.1 %, p = 0.001), while the rate of severe permanent renal toxicities was similar in both treatment groups (9.2 vs 7.8 %, p = 0.32). The present results revealed no difference in median overall survival after [{sup 177}Lu-DOTA]-TOC and [{sup 90}Y-DOTA]-TOC. Furthermore, [{sup 177}Lu-DOTA]-TOC was less haematotoxic than [{sup 90}Y-DOTA]-TOC. (orig.)

  13. {sup 68}Ga-Autoclabeling of DOTA-TATE and DOTA-NOC

    Energy Technology Data Exchange (ETDEWEB)

    Blom, Elisabeth [Department of Clinical Physiology, 54 P1, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev (Denmark); Koziorowski, Jacek, E-mail: jacek@heh.regionh.dk [Department of Clinical Physiology, 54 P1, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev (Denmark)

    2012-06-15

    Introduction: A new method combining {sup 68}Ga-labeling and steam sterilization, here called autoclabeling, has been evaluated for two somatostatin receptor binding tracers used for positron emission tomography (PET) imaging of neuroendocrine tumors; DOTA-TATE and -NOC. Methods: The two peptides DOTA-TATE and -NOC were labeled with {sup 68}Ga by heating for 15 min at 121 Degree-Sign C in the presence of acetate buffer at pH 4.3. The product solutions were tested for sterility, presence of endotoxins, degradation of peptide and osmolality. Results: Complete incorporation of {sup 68}Ga was obtained after the autoclabeling reaction and no degradation of the peptides was observed. Sterility was verified and the presence of endotoxins was well within Ph. Eur limits (175IU/maximum injected volume). Conclusions: The autoclabeling method provides a convenient procedure for {sup 68}Ga-labeling by combining the labeling reaction and steam sterilization into one single step. - HighLights: Black-Right-Pointing-Pointer We present a one-pot, one-step reaction and sterilization procedure. Black-Right-Pointing-Pointer The final product is isotonic and suitable for intravenous injection. Black-Right-Pointing-Pointer Total production time, handling and personell dose is minimized. Black-Right-Pointing-Pointer Validated and in accordance with Ph. Eur.

  14. 68Ga-Autoclabeling of DOTA-TATE and DOTA-NOC

    International Nuclear Information System (INIS)

    Introduction: A new method combining 68Ga-labeling and steam sterilization, here called autoclabeling, has been evaluated for two somatostatin receptor binding tracers used for positron emission tomography (PET) imaging of neuroendocrine tumors; DOTA-TATE and -NOC. Methods: The two peptides DOTA-TATE and -NOC were labeled with 68Ga by heating for 15 min at 121 °C in the presence of acetate buffer at pH 4.3. The product solutions were tested for sterility, presence of endotoxins, degradation of peptide and osmolality. Results: Complete incorporation of 68Ga was obtained after the autoclabeling reaction and no degradation of the peptides was observed. Sterility was verified and the presence of endotoxins was well within Ph. Eur limits (175IU/maximum injected volume). Conclusions: The autoclabeling method provides a convenient procedure for 68Ga-labeling by combining the labeling reaction and steam sterilization into one single step. - HighLights: ► We present a one-pot, one-step reaction and sterilization procedure. ► The final product is isotonic and suitable for intravenous injection. ► Total production time, handling and personell dose is minimized. ► Validated and in accordance with Ph. Eur.

  15. Quantification of acidic compounds in complex biomass-derived streams

    Energy Technology Data Exchange (ETDEWEB)

    Karp, Eric M.; Nimlos, Claire T.; Deutch, Steve; Salvachúa, Davinia; Cywar, Robin M.; Beckham, Gregg T.

    2016-01-01

    Biomass-derived streams that contain acidic compounds from the degradation of lignin and polysaccharides (e.g. black liquor, pyrolysis oil, pyrolytic lignin, etc.) are chemically complex solutions prone to instability and degradation during analysis, making quantification of compounds within them challenging. Here we present a robust analytical method to quantify acidic compounds in complex biomass-derived mixtures using ion exchange, sample reconstitution in pyridine and derivatization with BSTFA. The procedure is based on an earlier method originally reported for kraft black liquors and, in this work, is applied to identify and quantify a large slate of acidic compounds in corn stover derived alkaline pretreatment liquor (APL) as a function of pretreatment severity. Analysis of the samples is conducted with GCxGC-TOFMS to achieve good resolution of the components within the complex mixture. The results reveal the dominant low molecular weight components and their concentrations as a function of pretreatment severity. Application of this method is also demonstrated in the context of lignin conversion technologies by applying it to track the microbial conversion of an APL substrate. Here too excellent results are achieved, and the appearance and disappearance of compounds is observed in agreement with the known metabolic pathways of two bacteria, indicating the sample integrity was maintained throughout analysis. Finally, it is shown that this method applies more generally to lignin-rich materials by demonstrating its usefulness in analysis of pyrolysis oil and pyrolytic lignin.

  16. Branched-chain 2-keto acid decarboxylases derived from Psychrobacter.

    Science.gov (United States)

    Wei, Jiashi; Timler, Jacobe G; Knutson, Carolann M; Barney, Brett M

    2013-09-01

    The conversion of branched-chain amino acids to branched-chain acids or alcohols is an important aspect of flavor in the food industry and is dependent on the Ehrlich pathway found in certain lactic acid bacteria. A key enzyme in the pathway, the 2-keto acid decarboxylase (KDC), is also of interest in biotechnology applications to produce small branched-chain alcohols that might serve as improved biofuels or other commodity feedstocks. This enzyme has been extensively studied in the model bacterium Lactococcus lactis, but is also found in other bacteria and higher organisms. In this report, distinct homologs of the L. lactis KDC originally annotated as pyruvate decarboxylases from Psychrobacter cryohalolentis K5 and P. arcticus 273-4 were cloned and characterized, confirming a related activity toward specific branched-chain 2-keto acids derived from branched-chain amino acids. Further, KDC activity was confirmed in intact cells and cell-free extracts of P. cryohalolentis K5 grown on both rich and defined media, indicating that the Ehrlich pathway may also be utilized in some psychrotrophs and psychrophiles. A comparison of the similarities and differences in the P. cryohalolentis K5 and P. arcticus 273-4 KDC activities to other bacterial KDCs is presented. PMID:23826991

  17. Magnetofluorescent micelles incorporating Dy(III)-DOTA as potential bimodal agents for optical and high field magnetic resonance imaging.

    Science.gov (United States)

    Harris, Michael; Vander Elst, Luce; Laurent, Sophie; Parac-Vogt, Tatjana N

    2016-03-21

    Dysprosium(iii) was coordinated to four 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) bisamide derivatives functionalized with amphiphilic p-dodecylaniline and p-tetradecylaniline in a differing cis- and trans-orientation. The complexes were assembled into mono-disperse micelles having size distribution maxima ranging from 10 to 15 nm and the magnetic and optical properties of the micelles were examined in detail. The micelles show characteristic Dy(iii) emission with quantum yields reaching 0.8%. The transverse relaxivity r2 per Dy(iii) ion at 500 MHz and 310 K reaches maximum values of ca. 20 s(-1) mM(-1) which is a large increase when compared to a value of 0.8 s(-1) mM(-1) observed for Dy(III)-DTPA. The micelles were stable in water when incubated at 37 °C for 1 week and showed no relaxivity decrease when measured in the presence of 4% (w/v) human serum albumin. The efficient T2 relaxation, especially at strong magnetic fields, is sustained by the high magnetic moment of the dysprosium(iii) ion, the coordination of water molecules and long rotational correlation times. PMID:26865457

  18. Evaluation of antioxidant properties of monoaromatic derivatives of pulvinic acids.

    Science.gov (United States)

    Habrant, Damien; Poigny, Stéphane; Ségur-Derai, Muriel; Brunel, Yves; Heurtaux, Benoît; Le Gall, Thierry; Strehle, Axelle; Saladin, Régis; Meunier, Stéphane; Mioskowski, Charles; Wagner, Alain

    2009-04-23

    The natural mushroom pigment Norbadione A and three other pulvinic acids were shown by our group to display very efficient antioxidant properties by comparison with a collection of potent molecules including catechols, flavonoids, stilbenes, or coumarins. Despite numerous publications on robust and straightforward synthetic access to pulvinic acids by us and others, no report has been made to unravel the structure-activity relationships that govern the striking antioxidant activity. Herein is presented the synthesis of 18 diverse pulvinic acid derivatives and the study of their radical scavenging capacities by four different assays. The influence of each of the two phenyl rings, of their substituents and of the lateral chain on the antioxidant properties, was explored to reveal a simplified structure of excellent activity. These results, along with the absence of cytotoxicity, make the synthesized compounds interesting to evaluate for several biological activities and especially for anti-inflammatory effects and skin protection against UV induced oxidative stress.

  19. Comparison of [131I]-Tyr3-octreotate and [131I]DOTA-Tyr3-octreotate: the effect of DOTA on the pharmacokinetics and stability

    International Nuclear Information System (INIS)

    The introduction of radiolabeled somatostatin analogs for peptide receptor imaging and therapy of neuroendocrine cancer have become a primary focus of interest in nuclear medicine. In this work we studied the possibility of preparing radioiodinated octreotate derivatives, with high stability and favourable kinetic in vivo, because 131I-iodide is most frequently used in therapeutic nuclear medicine and aviable. We studied molar peptide to radionuclide ratio in order to obtain the mono-iodinated peptide (di-iodinated no longer binds to the somatostatin receptor). Like other radioiodinated proteins labeled on constituent tyrosine residues, it was important to study the possibility of dehalogenation in vivo. Despite DOTA chelating group was not necessary to the radioiodination procedure, we intended to evaluate the influence of the chelating group on the pharmacokinetic and the in vivo stability of the labeled peptide. 131I radiolabeling of Tyr3-octreotate and DOTA-Tyr3-octreotate was performed using Chloramine T method. A solution of 10 μg of peptide/40 μL of PBS (0.05M phosphate-buffered saline pH 7.5) was transferred to an Eppendorf cap. After addition of 10 μL (74 MBq) radioiodine and 5 μL of chloramine T solution (1mg/mL PBS), the cap was carefully stirred and the labeling reaction was allowed to proceed for 3 minutes at room temperature; 5 μL of sodium methabisulfite solution (2mg/mL PBS) was introduced as reducing agent. Radiochemical purity was determined by HPLC (Waters) using a RP C18 column (4.2 x 50 mm, 5 μm, Waters) with UV (230 nm) and radioactivity (Packard Canberra) detection, flow rate of 0.5 mL/minute with a linear gradient of 40-80% (v/v) methanol in 50 mM sodium acetate buffer (pH 5.5) for 20 minutes, maintained for another 25 minutes. Free radioiodine was also determined by horizontal zone electrophoresis (Amershan Pharmacia) on Whatman 1 paper, 0.05M barbital buffer, pH 8.6, 300V, 40 minutes. The stability of the compounds were evaluated

  20. Development of high-specific-activity 68Ga-labeled DOTA-rhenium-cyclized α-MSH peptide analog to target MC1 receptors overexpressed by melanoma tumors

    International Nuclear Information System (INIS)

    Introduction: A previous report on 68Ga-1,4,7,10-tetraazacyclodedecane-N,N',N'',N'''-tetraacetic acid (DOTA)-Re(Arg11)CCMSH was shown to indicate the imaging agent's potency for early detection of metastatic melanoma. However, the main limiting factor to developing high-specific-activity 68Ga-DOTA-Re(Arg11)CCMSH is the short half-life of 68Ga, which precludes further purification of the agent. To circumvent this problem, we incorporated the microwave technique to rapidly radiolabel the peptide with 68Ga, thereby allowing enough time to include high-performance liquid chromatography (HPLC) purification in the overall procedure. Methods: DOTA-Re(Arg11)CCMSH was radiolabeled with 68Ga in 68Ga-DOTA-Re(Arg11)CCMSH was then administered on B16/F1 murine melanoma-bearing C57 mice to study its biodistribution and positron emission tomography (PET) imaging capability. Results: The production of high-specific-activity 68Ga-DOTA-Re(Arg11)CCMSH resulted in an improved tumor uptake [6.93±1.11%ID/g at 30 min postinjection (p.i.) and 6.27±1.60%ID/g at 1 h p.i.] and tumor retention (5.85±1.32%ID/g at 4 h p.i.). Receptor-mediated tumor uptake was verified by blocking studies. Furthermore, high-resolution PET images of the tumor were obtained, owing to high tumor-to-nontarget organ ratios at an early time point (i.e., at 1 h biodistribution: tumor/blood, 14.3; tumor/muscle, 89.6; tumor/skin, 12.3) and fast clearance of the labeled peptide from kidney and other healthy tissues. Conclusion: High-specific-activity 68Ga-DOTA-Re(Arg11)CCMSH may have a potential role in the early diagnosis of metastasized melanoma.

  1. Postaurical injection is a systemic delivery supported by symmetric distribution of Gd-DOTA in both the ipsilateral and contralateral ears☆

    Institute of Scientific and Technical Information of China (English)

    Jing Zou

    2015-01-01

    Postaurical injection of therapeutics was recently applied in clinical practice to treat inner ear diseases based on supposed existence of a direct channel from the postaurical area to the inner ear. Doubting on the associated reports and aiming to provide evidence on the inner ear uptake mechanism, the present study tracked the dynamic distribution of gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (Gd-DOTA) in rat inner ears after postaurical injection using MRI. A targeted tympanic medial wall delivery was utilized as control. The results showed that, at the early time points after postaurical injection, Gd-DOTA distributed mainly in tissues surrounding the bulla, temporal bone and skull and neck space. In the inner ear, there was gradual uptake of Gd-DOTA on both the ipsilateral and contralateral sides with equal signal intensities. There was no sign of direct channel carrying the agent from the postaurical area to the inner ear. Targeted tympanic medial wall delivery induced significantly greater uptake of Gd-DOTA in the inner ear than did postaurical injection. At 30 min post-administration, targeted tympanic medial wall delivery yielded 4.6-folds higher signal intensity than did postaurical injection. The total dose of Gd-DOTA delivered by the targeted tympanic medial wall approach was only 0.1% of that delivered by postaurical injection. In conclusion, postaurical injection is a systemic administration, which is similar to hypodermic injection, rather than a focal delivery method. By contraries, targeted tympanic medial wall delivery induces fast and abundant uptake of Gd-DOTA in the ipsilateral inner ear without significant distribution in unwanted areas.

  2. Topology of Legionella pneumophila DotA: an inner membrane protein required for replication in macrophages.

    OpenAIRE

    Roy, C R; Isberg, R R

    1997-01-01

    The Legionella pneumophila dotA gene is required for intracellular growth of the bacterium in macrophages. In this study, a structure-function analysis of the DotA protein was conducted to elucidate the role of this protein in L. pneumophila pathogenesis. Translational fusions of dotA to the Escherichia coli phoA and lacZ genes indicated that DotA is an integral cytoplasmic membrane protein with eight membrane-spanning domains. DotA contains two large periplasmic domains of approximately 503 ...

  3. Determination of peptide content of DOTA-peptides by metal titration and UPLC

    International Nuclear Information System (INIS)

    Radiolabelled DOTA-peptides are in use for Peptide Receptor Radionuclide Scintigraphy (PRS) and Therapy (PRRT), e.g with 177Lu-DOTA-TATE or 90Y-DOTATOC. Labelling conditions are frequently critical. Therefore, the ingredients of the reaction, e.g. radiometal (90Y and 177Lu) and DOTA-peptide should be pure and the content known. Quality control of DOTA-peptide, can be performed with various methods, most commonly by UV. There are numerous conditions in which this is hampered, e.g. impurities may also have UV-absorption. The aim of the study was to quantify content and purity of DOTA-peptide

  4. Result Prediction by Mining Replays in Dota 2

    OpenAIRE

    Johansson, Filip; Wikström, Jesper

    2015-01-01

    Context: Real-time games like Dota 2 lack the extensive mathematical modeling of turn-based games that can be used to make objective statements about how to best play them. Understanding a real-time computer game through the same kind of modeling as a turn-based game is practically impossible. Objectives: In this thesis an attempt was made to create a model using machine learning that can predict the winning team of a Dota 2 game given partial data collected as the game progressed. A couple o...

  5. Preparation & in vitro evaluation of 90Y-DOTA-rituximab

    OpenAIRE

    Mythili Kameswaran; Usha Pandey; Ashutosh Dash; Grace Samuel; Meera Venkatesh

    2016-01-01

    Background & objectives: Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin′s lymphoma (NHL). Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA) to rituximab, its radiolabelling with [90] Y and in vitro and in vivo ev...

  6. Injectable hydrogels derived from phosphorylated alginic acid calcium complexes

    International Nuclear Information System (INIS)

    Phosphorylation of sodium alginate salt (NaAlg) was carried out using H3PO4/P2O5/Et3PO4 followed by acid–base reaction with Ca(OAc)2 to give phosphorylated alginic acid calcium complexes (CaPAlg), as a water dispersible alginic acid derivative. The modified alginate derivatives including phosphorylated alginic acid (PAlg) and CaPAlg were characterized by nuclear magnetic resonance spectroscopy for 1H, and 31P nuclei, high resolution inductively coupled plasma optical emission spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. CaPAlg hydrogels were prepared simply by mixing CaPAlg solution (2 w/v%) with NaAlg solution (2 w/v%) in various ratios (2:8, 4:6, 6:4, 8:2) of volume. No additional calcium salts such as CaSO4 or CaCl2 were added externally. The gelation was completed within about 3–40 min indicating a high potential of hydrogel delivery by injection in vivo. Their mechanical properties were tested to be ≤ 6.7 kPa for compressive strength at break and about 8.4 kPa/mm for elastic modulus. SEM analysis of the CaPAlg hydrogels showed highly porous morphology with interconnected pores of width in the range of 100–800 μm. Cell culture results showed that the injectable hydrogels exhibited comparable properties to the pure alginate hydrogel in terms of cytotoxicity and 3D encapsulation of cells for a short time period. The developed injectable hydrogels showed suitable physicochemical and mechanical properties for injection in vivo, and could therefore be beneficial for the field of soft tissue engineering. - Highlights: • Preparation of water-soluble alginic acid complexes with calcium phosphate • Self-assembly of the phosphorylated alginic acid calcium complexes with sodium alginate • Preparation of injectable hydrogels with diverse gelation times within about 3–40 min

  7. Biarylalkyl Carboxylic Acid Derivatives as Novel Antischistosomal Agents.

    Science.gov (United States)

    Mäder, Patrick; Blohm, Ariane S; Quack, Thomas; Lange-Grünweller, Kerstin; Grünweller, Arnold; Hartmann, Roland K; Grevelding, Christoph G; Schlitzer, Martin

    2016-07-01

    Parasitic platyhelminths are responsible for serious infectious diseases, such as schistosomiasis, which affect humans as well as animals across vast regions of the world. The drug arsenal available for the treatment of these diseases is limited; for example, praziquantel is the only drug currently used to treat ≥240 million people each year infected with Schistosoma spp., and there is justified concern about the emergence of drug resistance. In this study, we screened biarylalkyl carboxylic acid derivatives for their antischistosomal activity against S. mansoni. These compounds showed significant influence on egg production, pairing stability, and vitality. Tegumental lesions or gut dilatation was also observed. Substitution of the terminal phenyl residue in the biaryl scaffold with a 3-hydroxy moiety and derivatization of the terminal carboxylic acid scaffold with carboxamides yielded compounds that displayed significant antischistosomal activity at concentrations as low as 10 μm with satisfying cytotoxicity values. The present study provides detailed insight into the structure-activity relationships of biarylalkyl carboxylic acid derivatives and thereby paves the way for a new drug-hit moiety for fighting schistosomiasis. PMID:27159334

  8. Novel sustainable polymers derived from renewable rosin and fatty acids

    Science.gov (United States)

    Wilbon, Perry

    In the work of this dissertation, polymers derived from renewable bio-based resources prepared by various polymerization techniques were investigated. The properties of these polymeric materials were characterized and discussed. Rosin was first converted into acrylate or methacrylate monomers for atom transfer radical polymerization (ATRP). Second, rosin was combined with vegetable oil to produce completely renewable novel polyesters by acyclic diene metathesis (ADMET) polymerization. Third, degradable block copolymers were synthesized composed of polycaprolactone and rosin grafted polycaprolactone with the aid of ring-opening polymerization (ROP). Finally, degradable polyesters were produced using vegetable oil derivatives as starting materials. These new rosin and fatty acid based renewable polymer materials will have potential applications as sustainable thermoplastics, thermoplastic elastomers, etc.

  9. Inhibition of acidic corrosion of aluminum by triazoline derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Khamis, E. (Alexandria Univ., Ibrahimia (Egypt). Dept. of Chemistry); Atea, M. (Alexandria Univ., Ibrahimia (Egypt). Dept. of Materials Science)

    1994-02-01

    Inhibition of the corrosion of aluminum (Al) in hydrochloric acid (HCl) by some triazoline derivatives was studied in relation to the concentration of the inhibitors using gasometry, the weight-loss method, and the potentiodynamic technique. All compounds investigated were found to be inhibitors of the mixed type. The inhibitory character of the additives depended upon the +R (resonance) and +I (inductive) powers of alkyl or aryl groups of the triazoline derivatives. Inhibition was ascribed to the adsorption of the inhibitor onto the metal oxide surface following the Flory-Huggins isotherm. The compounds were adsorbed on the metal surface. Each molecule of the inhibitors occupied an average of 3.8 active sites on the metal surface. The values of activation free energies varied between [minus]30 kJ/mol and [minus]45 kJ/mol.

  10. A novel polymeric herbicide based on phenoxyacetic acid derivatives

    Directory of Open Access Journals (Sweden)

    Wimol Klaichim

    2009-01-01

    Full Text Available A novel polymeric herbicide based on phenoxyacetic acid derivatives was prepared by the reaction of epoxidised liquid natural rubber (ELNR with 2,4-dichlorophenoxyacetic acid (2,4-D or 2-methyl-4-chlorophenoxyacetic acid(MCPA. The liquid natural rubber (LNR was firstly obtained from the degradation of natural rubber latex with tert-butyl hydroperoxide and cobalt acetylacetonate at 65oC for 72 hrs. The epoxidised liquid natural rubber was prepared from thereaction of LNR with formic acid and hydrogen peroxide at 50oC for 6 hrs. The reaction of epoxidised liquid natural rubber with 2,4-D or MCPA using triethylamine as a catalyst in toluene was performed at 70, 80, and 90oC for 6, 9, 12, 18, and 24hrs. The polymeric herbicides obtained were characterized and the grafting percentage of 2,4-D or MCPA onto liquid natural rubber were also determined by FT-IR and 1H-NMR spectroscopy. It was found that the grafting percentage increased with increasing amount of reactants, temperature, and reaction time. The release of 2,4-D and MCPA from polymeric herbicides was investigated in pH 6, 7, and 8 buffers at room temperature. The results show that the slowest release of 2,4-D and MCPA was found to be constant at pH 7 for 14 and 10 days, respectively.

  11. Banana-shaped molecules derived from substituted isophthalic acids

    Indian Academy of Sciences (India)

    H T Nguyen; J P Bedel; J C Rouillon; J P Marcerou; M F Achard

    2003-08-01

    In this paper we present a review of five-rings banana-shaped molecules derived from isophthalic acids. This study deals with about a hundred compounds and most of them have not been published. By a combination of several linking groups and different selected substituents either on the outer rings or on the central core, several mesophases with switching properties are induced. The study of homologous series underlines the importance of the length and nature of the terminal chains. X-ray analysis reveals several new structures.

  12. Efficient Debromination of Vicinal (, (-Dibromo Carboxylic Acid Derivatives with the Sm/HOAc System

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The α, β vicinal dibromo carboxylic acid and its derivatives were debrominated with Sm/HOAc system to afford the corresponding cinnamic acid and its derivatives in good yields under mild conditions.

  13. Cinnamic Acid and Its Derivatives Inhibit Fructose-Mediated Protein Glycation

    OpenAIRE

    Sirintorn Yibchok-anun; Sirichai Adisakwattana; Weerachat Sompong; Sathaporn Ngamukote; Aramsri Meeprom

    2012-01-01

    Cinnamic acid and its derivatives have shown a variety of pharmacologic properties. However, little is known about the antiglycation properties of cinnamic acid and its derivatives. The present study sought to characterize the protein glycation inhibitory activity of cinnamic acid and its derivatives in a bovine serum albumin (BSA)/fructose system. The results demonstrated that cinnamic acid and its derivatives significantly inhibited the formation of advanced glycation end products (AGEs) by...

  14. Comparative biodistributions and dosimetry of [177Lu]DOTA-anti-bcl-2-PNA-Tyr3-octreotate and [177Lu]DOTA-Tyr3-octreotate in a mouse model of B-cell lymphoma/leukemia

    International Nuclear Information System (INIS)

    Introduction: The B-cell lymphoma/leukemia-2 (bcl-2) proto-oncogene in non-Hodgkin’s lymphoma (NHL) is a dominant inhibitor of apoptosis. We developed a 177Lu-labeled bcl-2 antisense peptide nucleic acid (PNA)–peptide conjugate designed for dual modality NHL therapy, consisting of a radiopharmaceutical capable of simultaneously down-regulating apoptotic resistance and delivering cytotoxic internally emitted radiation. Methods: DOTA-anti-bcl-2-Tyr3-octreotate was synthesized, labeled with 177Lu, and purified using RP-HPLC. The PNA–peptide conjugate was evaluated in Mec-1 NHL-bearing mice and compared to [177Lu]DOTA-Tyr3-octreotate in biodistribution and excretion studies. These data were then used to generate in vivo dosimetry models. Results: The PNA–peptide conjugate was readily prepared and radiolabeled in high yield and radiochemical purity. An in vivo blocking study determined that administration of 50 μg of non-radioactive PNA–peptide was the optimal mass for maximum delivery to the tumor. Based on that result, a dosing regimen of 177Lu-PNA–peptide, for radiologic effect, followed by the optimal mass of non-radioactive compound, for antisense effect, was designed. Using that dosing regimen, biodistribution of the PNA–peptide showed uptake in the tumor with minimal washout over a 4-day period. Uptakes in receptor-positive normal organs were low and displayed nearly complete washout by 24 h. Dosimetry models showed that the tumor absorbed dose of the PNA–peptide conjugate was approximately twice that of the peptide-only conjugate. Conclusions: Biodistribution data showed specific tumor targeting of the 177Lu-labeled PNA–peptide compound with minimal receptor-positive normal tissue uptake when compared to [177Lu]DOTA-Tyr3-octreotate. In vivo dosimetry models predicted a more favorable tumor absorbed dose from [177Lu]DOTA-anti-bcl-2-Tyr3-octreotate

  15. Procedure guidelines for PET/CT tumour imaging with 68Ga-DOTA-conjugated peptides: 68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE.

    NARCIS (Netherlands)

    Virgolini, I.; Ambrosini, V.; Bomanji, J.B.; Baum, R.P.; Fanti, S.; Gabriel, M.; Papathanasiou, N.D.; Pepe, G.; Oyen, W.J.G.; Cristoforo, C. De; Chiti, A.

    2010-01-01

    The aim of these guidelines is to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of somatostatin (SST) receptor PET/CT imaging using 68Ga-DOTA-conjugated peptides, analogues of octreotide, that bind to SST receptors. This imaging modality shoul

  16. Derivatives of xanthic acid are novel antioxidants: application to synaptosomes.

    Science.gov (United States)

    Lauderback, Christopher M; Drake, Jennifer; Zhou, Daohong; Hackett, Janna M; Castegna, Alessandra; Kanski, Jaroslaw; Tsoras, Maria; Varadarajan, Sridhar; Butterfield, D Allan

    2003-04-01

    Xanthic acids have long been known to act as reducing agents. Recently, D609, a tricyclodecanol derivative of xanthic acid, has been reported to have anti-apoptotic and anti-inflammatory properties that are attributed to specific inhibition of phosphatidyl choline phospholipase C (PC-PLC). However, because oxidative stress is involved in both of these cellular responses, the possibility that xanthates may act as antioxidants was investigated in the current study. Finding that xanthates efficiently scavenge hydroxyl radicals, the mechanism by which D609 and other xanthate derivatives may protect against oxidative damage was further examined. The xanthates studied, especially D609, mimic glutathione (GSH). Xanthates scavenge hydroxyl radicals and hydrogen peroxide, form disulfide bonds (dixanthogens), and react with electrophilic products of lipid oxidation (acrolein) in a manner similar to GSH. Further, upon disulfide formation, dixanthogens are reduced by glutathione reductase to a redox active xanthate. Supporting its role as an antioxidant, D609 significantly (p < 0.01) reduces free radical-induced changes in synaptosomal lipid peroxidation (TBARs), protein oxidation (protein carbonyls), and protein conformation. Thus, in addition to inhibitory effects on PC-PLC, D609 may prevent cellular apoptotic and inflammatory cascades by acting as antioxidants and novel GSH mimics. These results are discussed with reference to potential therapeutic application of D609 in oxidative stress conditions.

  17. Infrared Spectroscopy of Hydrogen Bonds in Benzoic Acid Derivatives

    Science.gov (United States)

    Tolstorozhev, G. B.; Bel‧kov, M. V.; Skornyakov, I. V.; Bazyl, O. K.; Artyukhov, V. Ya.; Mayer, G. V.; Shadyro, O. I.; Kuzovkov, P. V.; Brinkevich, S. D.; Samovich, S. N.

    2014-03-01

    We have measured the Fourier transform IR spectra of CCl4 solutions of benzoic acid and its biologically active derivatives. We investigated the proton-acceptor properties of the studied molecules theoretically by the molecular electrostatic potential method. The calculations are compared with experimental results. Based on an estimate of the proton-acceptor properties, we give an interpretation of the specific features of the IR spectra of benzoic acid and its derivatives in the region of the O-H and C = O vibrations. The mechanisms for interactions of the molecules are determined by the nature of substituents which are added to the benzene ring in positions para and meta to the carboxyl group. We identify the conditions for appearance of intermolecular hydrogen bonds of O-H · · · O = C, O-H · · · O-H types with formation of cyclic and linear dimers. We show that intramolecular hydrogen bonds of the type O-H · · · O-CH3 prevent the hydroxyl groups from participating in intermolecular interactions.

  18. Synthesis and antimicrobial activities of new higher amino acid Schiff base derivatives of 6-aminopenicillanic acid and 7-aminocephalosporanic acid

    Science.gov (United States)

    Özdemir (nee Güngör), Özlem; Gürkan, Perihan; Özçelik, Berrin; Oyardı, Özlem

    2016-02-01

    Novel β-lactam derivatives (1c-3c) (1d-3d) were produced by using 6-aminopenicillanic acid (6-APA), 7-aminocephalosporanic acid (7-ACA) and the higher amino acid Schiff bases. The synthesized compounds were characterized by elemental analysis, IR, 1H/13C NMR and UV-vis spectra. Antibacterial activities of all the higher amino acid Schiff bases (1a-3a) (1b-3b) and β-lactam derivatives were screened against three gram negative bacteria (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Acinetobacter baumannii RSKK 02026), three gram positive bacteria (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 07005, Bacillus subtilis ATCC 6633) and their drug-resistant isolates by using broth microdilution method. Two fungi (Candida albicans and Candida krusei) were used for antifungal activity.

  19. Tumor targeting using {sup 67}Ga-DOTA-Bz-folate - investigations of methods to improve the tissue distribution of radiofolates

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Cristina, E-mail: cristina.mueller@psi.ch [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Vlahov, Iontcho R.; Santhapuram, Hari Krishna R.; Leamon, Christopher P. [Endocyte Inc., West Lafayette, IN 47906 (United States); Schibli, Roger [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich (Switzerland)

    2011-07-15

    Introduction: Use of folic acid radioconjugates for folate receptor (FR) targeting is a promising strategy for imaging purposes as well as for potential therapy of cancer and inflammatory diseases due to the frequent FR overexpression found on cancer cells and activated macrophages. Herein, we report on preclinical results using a novel DOTA-Bz-EDA-folate conjugate radiolabeled with [{sup 67}Ga]-gallium. Methods: DOTA-Bz-EDA-folate was prepared by conjugation of ethylenediamine-({gamma})-folate with 2-(p-isothiocyanobenzyl)-DOTA. Radiolabeling was carried out with {sup 67}GaCl{sub 3} according to standard procedures. Biodistribution studies of the tracer were performed in mice bearing FR-positive KB tumor xenografts. The effects on radiofolate biodistribution with coadministered renal uptake-blocking amino acids, diuretic agents, antifolates as well as different routes of administration were likewise investigated. Supportive imaging studies were performed using a small-animal single photon emission computed tomography (SPECT)/CT scanner. Results: {sup 67}Ga-DOTA-Bz-EDA-folate showed a high and specific accumulation in tumors (6.30%{+-}0.75% ID/g, 1 h pi and 6.08%{+-}0.89% ID/g, 4 h pi). Nonspecific radioactivity uptake in nontargeted tissues was negligible, but significant accumulation was found in FR-positive kidneys, which resulted in unfavorably low tumor-to-kidney ratios (<0.1). Coadministered amino acids or diuretics did not effectively reduce renal accumulation; in contrast, predosed pemetrexed did significantly reduce kidney uptake (<29% of control values). The SPECT/CT studies confirmed the excellent tumor-to-background contrast of {sup 67}Ga-radiofolate and the favorable reduction in kidney uptake (with improved imaging quality) resulting from pemetrexed administration. Conclusion: Conventional methods to reduce kidney uptake of radiofolates fail. However, the novel {sup 67}Ga-radiolabeled DOTA-Bz-EDA-folate can effectively be used to image FR

  20. Injectable hydrogels derived from phosphorylated alginic acid calcium complexes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Han-Sem; Song, Minsoo, E-mail: minsoosong00@gmail.com; Lee, Eun-Jung; Shin, Ueon Sang, E-mail: usshin12@dankook.ac.kr

    2015-06-01

    Phosphorylation of sodium alginate salt (NaAlg) was carried out using H{sub 3}PO{sub 4}/P{sub 2}O{sub 5}/Et{sub 3}PO{sub 4} followed by acid–base reaction with Ca(OAc){sub 2} to give phosphorylated alginic acid calcium complexes (CaPAlg), as a water dispersible alginic acid derivative. The modified alginate derivatives including phosphorylated alginic acid (PAlg) and CaPAlg were characterized by nuclear magnetic resonance spectroscopy for {sup 1}H, and {sup 31}P nuclei, high resolution inductively coupled plasma optical emission spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. CaPAlg hydrogels were prepared simply by mixing CaPAlg solution (2 w/v%) with NaAlg solution (2 w/v%) in various ratios (2:8, 4:6, 6:4, 8:2) of volume. No additional calcium salts such as CaSO{sub 4} or CaCl{sub 2} were added externally. The gelation was completed within about 3–40 min indicating a high potential of hydrogel delivery by injection in vivo. Their mechanical properties were tested to be ≤ 6.7 kPa for compressive strength at break and about 8.4 kPa/mm for elastic modulus. SEM analysis of the CaPAlg hydrogels showed highly porous morphology with interconnected pores of width in the range of 100–800 μm. Cell culture results showed that the injectable hydrogels exhibited comparable properties to the pure alginate hydrogel in terms of cytotoxicity and 3D encapsulation of cells for a short time period. The developed injectable hydrogels showed suitable physicochemical and mechanical properties for injection in vivo, and could therefore be beneficial for the field of soft tissue engineering. - Highlights: • Preparation of water-soluble alginic acid complexes with calcium phosphate • Self-assembly of the phosphorylated alginic acid calcium complexes with sodium alginate • Preparation of injectable hydrogels with diverse gelation times within about 3–40 min.

  1. Tumour uptake of the radiolabelled somatostatin analogue [DOTA0,TYR3]octreotide is dependent on the peptide amount

    International Nuclear Information System (INIS)

    Radiolabelled tumour receptor-binding peptides can be used for in vivo scintigraphic imaging. Recently, the somatostatin analogue [Tyr3]octreotide (d-Phe-c(Cys-Tyr-d-Trp-Lys-Thr-Cys)-Thr(ol)) was derivatized with the chelator DOTA (tetra-azacyclododecane-tetra-acetic acid), enabling stable radiolabelling with both the high-energy beta particle-emitter yttrium-90 and the Auger electron-emitter indium-111. The thus produced radiolabelled compounds are promising for peptide receptor radionuclide therapy. Our previous in vitro and in vivo (rat) experiments with these radiolabelled compounds showed favourable binding and biodistribution characteristics with high uptake and retention in the target organs. We also demonstrated receptor-specific, time- and temperature-dependent internalization of radiolabelled [DOTA0,Tyr3]octreotide in somatostatin receptor subtype 2 (sst2)-positive rat pancreatic tumour cell lines. In this study we have investigated the effects of differences in the amount of injected peptide on tissue distribution of 111In-labelled [DOTA0,Tyr3]octreotide in normal, i.e. non-tumour-bearing, and CA20948 tumour-bearing rats. This was done in order to find the amount of peptide at which the highest uptake in target tissues is achieved, and thereby to increase the potential of radionuclide therapy while simultaneously ensuring the lowest possible radiotoxicity in normal organs. Uptake of radiolabelled [DOTA0,Tyr3]octreotide in sst2-positive organs showed different bell-shaped functions of the amount of injected peptide, being highest at 0.05 (adrenals), 0.05-0.1 (pituitary and stomach) and 0.25 (pancreas) μg. Uptake in the tumour was highest at 0.5 μg injected peptide. The highest uptake was found at peptide amounts that were lower than those reported for [111In-DTPA0]octreotide (d-Phe-c(Cys-Phe-d-Trp-Lys-Thr-Cys)-Thr(ol), DTPA = diethylene-triamine-penta-acetic acid), consistent with the higher receptor affinity of the first compound. Our observations of

  2. TWO BIOACTIVE FERULIC ACID DERIVATIVES FROM EREMOSTACHYS GLABRA

    Directory of Open Access Journals (Sweden)

    Abbas Delazar

    2004-07-01

    Full Text Available Two ferulic acid derivatives, hexacosyl-(E-ferulate [1] and leucosceptoside A [2], have been isolated from the rhizomes of Eremostachys glabra. The chemical structures of these compounds have been elucidated by UV, ESIMS, 1H NMR and 13C NMR spectroscopic analyses, and also by comparing experimental data with respective literature data. The free radical scavenging activity and general toxicity of these compounds have been assessed. While none of these compounds has shown any significant general toxicity in the brine shrimp lethality assay (LD50>1 mg/mL, compounds 1 and 2 displayed significant antioxidant activity in the DPPH assay (RC50 = 0.0976 mg/mL and 0.0148 mg/mL, respectively.

  3. Study of Thiosemicarbazone Derivative of Essential Fatty Acid

    OpenAIRE

    Borhade, Shobha

    2014-01-01

    Essential fatty acids results in numerous health benefits. Only two fatty acids are known to be essential for human alpha-linolenic acid (an omega-3 fatty acid) and linoleic acid (an omega-6 fatty acid).The importance of omega-3 fatty acids for physical well-being has been recognised for several decades . Omega-3 fatty acids have anti-inflammatory, antithrombotic, antiarrhythmic and hypolipidaemic effects. Cannabis sativa (Hemp) is an angiosperm belonging to the cannabaceae family and cannabi...

  4. Somatostatin receptor PET in neuroendocrine tumours: {sup 68}Ga-DOTA{sup 0},Tyr{sup 3}-octreotide versus {sup 68}Ga-DOTA{sup 0}-lanreotide

    Energy Technology Data Exchange (ETDEWEB)

    Putzer, Daniel; Kroiss, Alexander; Waitz, Dietmar; Gabriel, Michael; Uprimny, Christian; Guggenberg, Elisabeth von; Decristoforo, Clemens; Warwitz, Boris; Virgolini, Irene Johanna [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); Traub-Weidinger, Tatjana [Vienna Medical University, Department of Nuclear Medicine, Vienna (Austria); Widmann, Gerlig [Innsbruck Medical University, Department of Radiology, Innsbruck (Austria)

    2013-03-15

    The aim of this study was to evaluate the impact of {sup 68}Ga-labelled DOTA{sup 0}-lanreotide ({sup 68}Ga-DOTA-LAN) on the diagnostic assessment of neuroendocrine tumour (NET) patients with low to moderate uptake on planar somatostatin receptor (SSTR) scintigraphy or {sup 68}Ga-labelled DOTA{sup 0},Tyr{sup 3}-octreotide ({sup 68}Ga-DOTA-TOC) positron emission tomography (PET). Fifty-three patients with histologically confirmed NET and clinical signs of progressive disease, who had not qualified for peptide receptor radionuclide therapy (PRRT) on planar SSTR scintigraphy or {sup 68}Ga-DOTA-TOC PET (n = 38) due to lack of tracer uptake, underwent {sup 68}Ga-DOTA-LAN PET to evaluate a treatment option with {sup 90}Y-labelled lanreotide according to the MAURITIUS trial. The included patients received 150 {+-} 30 MBq of each radiopharmaceutical intravenously. PET scans were acquired 60-90 min after intravenous bolus injection. Image results from both PET scans were compared head to head, focusing on the intensity of tracer uptake in terms of treatment decision. CT was used for morphologic correlation of tumour lesions. To further evaluate the binding affinities of each tracer, quantitative and qualitative values were calculated for target lesions. {sup 68}Ga-DOTA-LAN and {sup 68}Ga-DOTA-TOC both showed equivalent findings in 24/38 patients when fused PET/CT images were interpreted. The sensitivity, specificity and accuracy of {sup 68}Ga-DOTA-LAN in comparison to CT were 0.63, 0.5 and 0.62 (n = 53; p < 0.0001) and for {sup 68}Ga-DOTA-TOC in comparison to CT 0.78, 0.5 and 0.76 (n = 38; p < 0.013), respectively. {sup 68}Ga-DOTA-TOC showed a significantly higher maximum standardized uptake value (SUV{sub max}) regarding the primary tumour in 25 patients (p < 0.003) and regarding the liver in 30 patients (p < 0.009) compared to {sup 68}Ga-DOTA-LAN. Corresponding values of both PET scans for tumour and liver did not show any significant correlation. {sup 68}Ga-DOTA

  5. Gallic acid and gallic acid derivatives: effects on drug metabolizing enzymes.

    Science.gov (United States)

    Ow, Yin-Yin; Stupans, Ieva

    2003-06-01

    Gallic acid and its structurally related compounds are found widely distributed in fruits and plants. Gallic acid, and its catechin derivatives are also present as one of the main phenolic components of both black and green tea. Esters of gallic acid have a diverse range of industrial uses, as antioxidants in food, in cosmetics and in the pharmaceutical industry. In addition, gallic acid is employed as a source material for inks, paints and colour developers. Studies utilising these compounds have found them to possess many potential therapeutic properties including anti-cancer and antimicrobial properties. In this review, studies of the effects of gallic acid, its esters, and gallic acid catechin derivatives on Phase I and Phase II enzymes are examined. Many published reports of the effects of the in vitro effects of gallic acid and its derivatives on drug metabolising enzymes concern effects directly on substrate (generally drug or mutagen) metabolism or indirectly through observed effects in Ames tests. In the case of the Ames test an antimutagenic effect may be observed through inhibition of CYP activation of indirectly acting mutagens and/or by scavenging of metabolically generated mutagenic electrophiles. There has been considerable interest in the in vivo effects of the gallate esters because of their incorporation into foodstuffs as antioxidants and in the catechin gallates with their potential role as chemoprotective agents. Principally an induction of Phase II enzymes has been observed however more recent studies using HepG2 cells and primary cultures of human hepatocytes provide evidence for the overall complexity of actions of individual components versus complex mixtures, such as those in food. Further systematic studies of mechanisms of induction and inhibition of drug metabolising enzymes by this group of compounds are warranted in the light of their distribution and consequent ingestion, current uses and suggested therapeutic potential. However, it

  6. Pre-therapeutic dosimetry and biodistribution of 86Y-DOTA-Phe1-Tyr3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours

    International Nuclear Information System (INIS)

    For the internal radiotherapy of neuroendocrine tumours, the somatostatin analogue DOTATOC labelled with 90Y is frequently used [90Y-DOTA-Phe1-Tyr3-octreotide (SMT487-OctreoTher)]. Radiation exposure to the kidneys is critical in this therapy as it may result in renal failure. The aim of this study was to compare cumulative organ and tumour doses based upon dosimetric data acquired with the chemically identical 86Y-DOTA-Phe1-Tyr3-octreotide (considered as the gold standard) and the commercially available 111In-pentetreotide. The cumulative organ and tumour doses for the therapeutic administration of 13.32 GBq 90Y-DOTA-Phe1-Tyr3-octreotide (three cycles, each of 4.44 GBq) were estimated based on the MIRD concept (MIRDOSE 3.1 and IMEDOSE). Patients with a cumulative kidney dose exceeding 27 Gy had to be excluded from subsequent therapy with 90Y-DOTA-Phe1-Tyr3-octreotide, in accordance with the directives of the German radiation protection authorities. The range of doses (mGy/MBq 90Y-DOTA-Phe1-Tyr3-octreotide) for kidneys, spleen, liver and tumour masses was 0.6-2.8, 1.5-4.2, 0.3-1.3 and 2.1-29.5 (86Y-DOTA-Phe1-Tyr3-octreotide), respectively, versus 1.3-3.0, 1.8-4.4, 0.2-0.8 and 1.4-19.7 (111In-pentetreotide), with wide inter-subject variability. Despite renal protection with amino acid infusions, estimated cumulative kidney doses in two patients exceeded 27 Gy. Compared with 86Y-DOTA-Phe1-Tyr3-octreotide, dosimetry with 111In-pentetreotide overestimated doses to kidneys and spleen, whereas the radiation dose to the tumour-free liver was underestimated. However, both dosimetric approaches detected the two patients with an exceptionally high radiation burden to the kidneys that carried a potential risk of renal failure following radionuclide therapy. (orig.)

  7. Synthesis of -acylurea derivatives from carboxylic acids and ,' -dialkyl carbodiimides in water

    Indian Academy of Sciences (India)

    Ali Ramazani; Fatemeh Zeinali Nasrabadi; Aram Rezaei; Morteza Rouhani; Hamideh Ahankar; Pegah Azimzadeh Asiabi; Sang Woo Joo; Katarzyna Ślepokura; Tadeusz Lis

    2015-12-01

    Reactions of benzoic acid derivatives and ()-cinnamic acid derivatives with , '-dialkyl carbodiimide proceed smoothly at room temperature and in neutral conditions to afford -acylurea derivatives in high yields. The reaction proceeds smoothly and cleanly under mild conditions and no side reactions were observed.

  8. Validation of 64Cu-DOTA-rituximab injection preparation under good manufacturing practices: a PET tracer for imaging of B-cell non-Hodgkin lymphoma.

    Science.gov (United States)

    Natarajan, Arutselvan; Arksey, Natasha; Iagaru, Andrei; Chin, Frederick T; Gambhir, Sanjiv Sam

    2015-01-01

    Manufacturing of 64Cu-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-rituximab injection under good manufacturing practices (GMP) was validated for imaging of patients with CD20+ B-cell non-Hodgkin lymphoma. Rituximab was purified by size exclusion high performance liquid chromatography (HPLC) and conjugated to DOTA-mono-(N-hydroxysuccinimidyl) ester. 64CuCl2, buffers, reagents, and other raw materials were obtained as high-grade quality. Following a semi-automated synthesis of 64Cu-DOTA-rituximab, a series of quality control tests was performed. The product was further tested in vivo using micro-positron emission tomography/computed tomography (PET/CT) to assess targeting ability towards human CD20 in transgenic mice. Three batches of 64Cu-DOTA-rituximab final product were prepared as per GMP specifications. The radiolabeling yield from these batches was 93.1 ± 5.8%; these provided final product with radiopharmaceutical yield, purity, and specific activity of 59.2 ± 5.1% (0.9 ± 0.1 GBq of 64Cu), > 95% (by HPLC and radio-thin layer chromatography), and 229.4 ± 43.3 GBq/µmol (or 1.5 ± 0.3 MBq/µg), respectively. The doses passed apyrogenicity and human serum stability specifications, were sterile up to 14 days, and retained > 60% immunoreactivity. In vivo micro-PET/CT mouse images at 24 hours postinjection showed that the tracer targeted the intended sites of human CD20 expression. Thus, we have validated the manufacturing of GMP grade 64Cu-DOTA-rituximab for injection in the clinical setting. PMID:25762106

  9. Prospective evaluation of 68Ga-DOTA-NOC PET-CT in phaeochromocytoma and paraganglioma: preliminary results from a single centre study

    International Nuclear Information System (INIS)

    To evaluate the role of 68Ga-labelled [1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid]-1-NaI3-Octreotide (68Ga-DOTA-NOC) whole body positron emission tomography-computed tomography (PET-CT) as a functional imaging approach for phaeochromocytoma and paraganglioma. Thirty-five unrelated patients (Median age-34.4 years; range: 15-71) were evaluated in this prospective study. PET-CT was performed after injection of 132-222 MBq of 68Ga-DOTA-NOC. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as quantitatively (standardised uptake value-SUVmax). In addition we compared the findings with 131I Metaiodobenzylguanidine (MIBG) scintigraphy, which was available for 25 patients. Histopathology and/or conventional imaging with biochemical markers were taken as the reference standard. 44 lesions were detected on 68Ga-DOTA-NOC PET-CT imaging with an additional detection of 12 lesions not previously known, leading to a change in management of 6 patients. Sensitivity, specificity and accuracy were 100%, 85.7%, and 97.1% on a per patient basis and 100%, 85.7% and 98% on per lesion basis, respectively.131I MIBG scintigraphy was concordant with 68Ga-DOTA-NOC PET-CT in 16 patients and false negative in 9 patients. 68Ga-DOTA-NOC PET-CT is highly sensitive and specific for the detection of phaeochromoctyomas and paragangliomas. It seems better than 131I MIBG scintigraphy for this purpose. (orig.)

  10. Prospective evaluation of {sup 68}Ga-DOTA-NOC PET-CT in phaeochromocytoma and paraganglioma: preliminary results from a single centre study

    Energy Technology Data Exchange (ETDEWEB)

    Naswa, Niraj; Sharma, Punit; Nazar, Aftab Hasan; Agarwal, Krishan Kant; Kumar, Rakesh; Malhotra, Arun; Bal, Chandrasekhar [All India Institute of Medical Sciences, Department of Nuclear Medicine, Ansari Nagar, New Delhi (India); Ammini, Ariachery C. [All India Institute of Medical Sciences, Department of Endocrinology and Metabolism, New Delhi (India)

    2012-03-15

    To evaluate the role of {sup 68}Ga-labelled [1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid]-1-NaI{sup 3}-Octreotide ({sup 68}Ga-DOTA-NOC) whole body positron emission tomography-computed tomography (PET-CT) as a functional imaging approach for phaeochromocytoma and paraganglioma. Thirty-five unrelated patients (Median age-34.4 years; range: 15-71) were evaluated in this prospective study. PET-CT was performed after injection of 132-222 MBq of {sup 68}Ga-DOTA-NOC. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as quantitatively (standardised uptake value-SUVmax). In addition we compared the findings with {sup 131}I Metaiodobenzylguanidine (MIBG) scintigraphy, which was available for 25 patients. Histopathology and/or conventional imaging with biochemical markers were taken as the reference standard. 44 lesions were detected on {sup 68}Ga-DOTA-NOC PET-CT imaging with an additional detection of 12 lesions not previously known, leading to a change in management of 6 patients. Sensitivity, specificity and accuracy were 100%, 85.7%, and 97.1% on a per patient basis and 100%, 85.7% and 98% on per lesion basis, respectively.{sup 131}I MIBG scintigraphy was concordant with {sup 68}Ga-DOTA-NOC PET-CT in 16 patients and false negative in 9 patients. {sup 68}Ga-DOTA-NOC PET-CT is highly sensitive and specific for the detection of phaeochromoctyomas and paragangliomas. It seems better than {sup 131}I MIBG scintigraphy for this purpose. (orig.)

  11. Investigation of molecular interactions in the complex formation of tartaric acid derivatives with di(2-ethylhexyl) phosphoric acid

    Institute of Scientific and Technical Information of China (English)

    TAN Bin; ZHAI Zheng; LUO GuangSheng; WANG JiaDing

    2008-01-01

    The molecular interactions in the complex formation of two tartaric acid derivatives with di(2-ethylhexyl) phosphoric acid are investigated. The complex formation with a 1:1 stoichiometry between tartaric acid derivatives and D2EHPA can be obtained through UV-Vis titration, NMR chemical shifts and molecular dynamic simulations. Furthermore, the differences of the two complexes on the binding constants and strength of hydrogen bonds can also be determined. Such research will ideally provide insight into ways of regulating the complex forming properties of tartaric acid derivatives for composing or syn-thesizing new chiral resolving agents.

  12. Investigation of molecular interactions in the complex formation of tartaric acid derivatives with di(2-ethylhexyl) phosphoric acid

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The molecular interactions in the complex formation of two tartaric acid derivatives with di(2-ethylhexyl) phosphoric acid are investigated. The complex formation with a 1:1 stoichiometry between tartaric acid derivatives and D2EHPA can be obtained through UV-Vis titration, NMR chemical shifts and molecular dynamic simulations. Furthermore, the differences of the two complexes on the binding constants and strength of hydrogen bonds can also be determined. Such research will ideally provide insight into ways of regulating the complex forming properties of tartaric acid derivatives for composing or syn- thesizing new chiral resolving agents.

  13. Cannabimimetic fatty acid derivatives in cancer and inflammation.

    Science.gov (United States)

    Di Marzo, V; Melck, D; De Petrocellis, L; Bisogno, T

    2000-04-01

    Evidence for the role of the cannabimimetic fatty acid derivatives (CFADs), i.e. anandamide (arachidonoylethanolamide, AEA), 2-arachidonoylglycerol (2-AG) and palmitoylethanolamide (PEA), in the control of inflammation and of the proliferation of tumor cells is reviewed here. The biosynthesis of AEA, PEA, or 2-AG can be induced by stimulation with either Ca(2+) ionophores, lipopolysaccharide, or platelet activating factor in macrophages, and by ionomycin or antigen challenge in rat basophilic leukemia (RBL-2H3) cells (a widely used model for mast cells). These cells also inactivate CFADs through re-uptake and/or hydrolysis and/or esterification processes. AEA and PEA modulate cytokine and/or arachidonate release from macrophages in vitro, regulate serotonin secretion from RBL-2H3 cells, and are analgesic in some animal models of inflammatory pain. However, the involvement of endogenous CFADs and cannabinoid CB(1) and CB(2) receptors in these effects is still controversial. In human breast and prostate cancer cells, AEA and 2-AG, but not PEA, potently inhibit prolactin and/or nerve growth factor (NGF)-induced cell proliferation. Vanillyl-derivatives of anandamide, such as olvanil and arvanil, exhibit even higher anti-proliferative activity. These effects are due to suppression of the levels of the 100 kDa prolactin receptor or of the high affinity NGF receptors (trk), are mediated by CB(1)-like cannabinoid receptors, and are enhanced by other CFADs. Inhibition of adenylyl cyclase and activation of mitogen-activated protein kinase underlie the anti-mitogenic actions of AEA. The possibility that CFADs act as local inhibitors of the proliferation of human breast cancer is discussed here. PMID:10785541

  14. Benzoic acid derivatives from Piper species and their antiparasitic activity.

    Science.gov (United States)

    Flores, Ninoska; Jiménez, Ignacio A; Giménez, Alberto; Ruiz, Grace; Gutiérrez, David; Bourdy, Genevieve; Bazzocchi, Isabel L

    2008-09-01

    Piper glabratum and P. acutifolium were analyzed for their content of main secondary constituents, affording nine new benzoic acid derivatives (1, 2, 4, 5, 7, and 10-13), in addition to four known compounds (3, 6, 8, and 9). Their structures were elucidated on the basis of spectroscopic data. Riguera ester reactions and optical rotation measurements established the new compounds as racemates. In the search for antiparasitic agents, the compounds were evaluated in vitro against the promastigote forms of Leishmania spp., Trypanosoma cruzi, and Plasmodium falciparum. Among the evaluated compounds, methyl 3,4-dihydroxy-5-(3'-methyl-2'-butenyl)benzoate (7) exhibited leishmanicidal effect (IC50 13.8-18.5 microg/mL) against the three Leishmania strains used, and methyl 3,4-dihydroxy-5-(2-hydroxy-3-methylbutenyl)benzoate (1), methyl 4-hydroxy-3-(2-hydroxy-3-methyl-3-butenyl)benzoate (3), and methyl 3,4-dihydroxy-5-(3-methyl-2-butenyl) benzoate (7) showed significant trypanocidal activity, with IC50 values of 16.4, 15.6, and 18.5 microg/mL, respectively. PMID:18712933

  15. Treatment with tandem [{sup 90}Y]DOTA-TATE and [{sup 177}Lu]DOTA-TATE of neuroendocrine tumours refractory to conventional therapy

    Energy Technology Data Exchange (ETDEWEB)

    Seregni, E.; Maccauro, M.; Chiesa, C.; Pascali, C.; Lorenzoni, A.; Bogni, A.; Coliva, A.; Bombardieri, E. [Fondazione IRCCS Istituto Nazionale Tumori, Nuclear Medicine, Milan (Italy); Mariani, L.; Vullo, S.Lo [Fondazione IRCCS Istituto Nazionale Tumori, Statistics and Biometry Unit, Milan (Italy); Mazzaferro, V. [Fondazione IRCCS Istituto Nazionale Tumori, Surgery and Liver Transplantation, Milan (Italy); De Braud, F.; Buzzoni, R. [Fondazione IRCCS Istituto Nazionale Tumori, Medical Oncology, Milan (Italy); Milione, M. [Fondazione IRCCS Istituto Nazionale Tumori, Pathology Department, Milan (Italy)

    2014-02-15

    Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues has been demonstrated to be an effective therapeutic option in patients with disseminated neuroendocrine tumours (NET). Treatment with tandem [{sup 90}Y]DOTA-TATE and [{sup 177}Lu]DOTA-TATE may improve the efficacy of PRRT without increasing the toxicity. In a phase II study we evaluated the feasibility of combined PPRT with a high-energy beta emitter ({sup 90}Y) and a medium-energy beta/gamma emitter ({sup 177}Lu) in patients with metastatic NET refractory to conventional therapy. A group of 26 patients with metastatic NET were treated with four therapeutic cycles of alternating [{sup 177}Lu]DOTA-TATE (5.55 GBq) and [{sup 90}Y]DOTA-TATE (2.6 GBq). A dosimetric evaluation was carried out after administration of [{sup 177}Lu]DOTA-TATE to calculate the absorbed doses in healthy organs. The acute and long-term toxicities of repeated treatment were analysed. PRRT efficacy was evaluated according to RECIST. Administration of tandem [{sup 90}Y]DOTA-TATE and [{sup 177}Lu]DOTA-TATE induced objective responses in 42.3 % of patients with metastatic NET with a median progression-free survival longer than 24 months. Of patients with pretreatment carcinoid syndrome, 90 % showed a symptomatic response or a reduction in tumour-associated pain. The cumulative biologically effective doses (BED) were below the toxicity limit in the majority of patients, in the absence of renal function impairment The results of our study indicates that combined [{sup 90}Y]DOTA-TATE and [{sup 177}Lu]DOTA-TATE therapy is a feasible and effective therapeutic option in NET refractory to conventional therapy. Furthermore, the absence of kidney damage and the evaluated cumulative BEDs suggest that increasing the number of tandem administrations is an interesting approach. (orig.)

  16. Treatment with tandem [90Y]DOTA-TATE and [177Lu]DOTA-TATE of neuroendocrine tumours refractory to conventional therapy

    International Nuclear Information System (INIS)

    Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues has been demonstrated to be an effective therapeutic option in patients with disseminated neuroendocrine tumours (NET). Treatment with tandem [90Y]DOTA-TATE and [177Lu]DOTA-TATE may improve the efficacy of PRRT without increasing the toxicity. In a phase II study we evaluated the feasibility of combined PPRT with a high-energy beta emitter (90Y) and a medium-energy beta/gamma emitter (177Lu) in patients with metastatic NET refractory to conventional therapy. A group of 26 patients with metastatic NET were treated with four therapeutic cycles of alternating [177Lu]DOTA-TATE (5.55 GBq) and [90Y]DOTA-TATE (2.6 GBq). A dosimetric evaluation was carried out after administration of [177Lu]DOTA-TATE to calculate the absorbed doses in healthy organs. The acute and long-term toxicities of repeated treatment were analysed. PRRT efficacy was evaluated according to RECIST. Administration of tandem [90Y]DOTA-TATE and [177Lu]DOTA-TATE induced objective responses in 42.3 % of patients with metastatic NET with a median progression-free survival longer than 24 months. Of patients with pretreatment carcinoid syndrome, 90 % showed a symptomatic response or a reduction in tumour-associated pain. The cumulative biologically effective doses (BED) were below the toxicity limit in the majority of patients, in the absence of renal function impairment The results of our study indicates that combined [90Y]DOTA-TATE and [177Lu]DOTA-TATE therapy is a feasible and effective therapeutic option in NET refractory to conventional therapy. Furthermore, the absence of kidney damage and the evaluated cumulative BEDs suggest that increasing the number of tandem administrations is an interesting approach. (orig.)

  17. Synthesis of novel (1-alkanoyloxy-4-alkanoylaminobutylidene)-1,1-bisphosphonic acid derivatives

    OpenAIRE

    Vepsäläinen Jouko J; Turhanen Petri A

    2006-01-01

    Abstract A novel strategy for the synthesis of (1-alkanoyloxy-4-alkanoylaminobutylidene)-1,1-bisphosphonic acid derivatives (1a-d) via (1-hydroxy-4-alkanoylaminobutylidene)-1,1-bisphosphonic acid derivatives (2a-d), starting from alendronate has been developed with reasonable 51–77% overall yields. Intermediate products, (1-hydroxy-4-alkanoylaminobutylidene)-1,1-bisphosphonic acid derivatives (2a-d), were prepared in water with reasonable to high yields (52–94%).

  18. The Synthesis of Some Novel N-[a-(Isoflavone-7-O-)Acetyl ] Amino Acid Derivatives

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A series of novel N-[(α)-(isoflavone-7-O-)acetyl] amino acid methyl esters were prepared from the efficient and regioselective alkylation of isoflavones with chloroacetyl amino acid derivatives under mild condition.

  19. Population Genetic Structure of Legionella pneumophila Inferred from RNA Polymerase Gene (rpoB) and DotA Gene (dotA) Sequences

    OpenAIRE

    Ko, Kwan Soo; Lee, Hae Kyung; Park, Mi-Yeoun; Park, Man-suk; Lee, Keun-Hwa; Woo, So-Yon; Yun, Yeo-Jun; Kook, Yoon-Hoh

    2002-01-01

    The population structure of Legionella pneumophila was studied by using partial RNA polymerase gene (rpoB) and DotA gene (dotA) sequences. Trees inferred from rpoB sequences showed that two subspecies of L. pneumophila, Legionella pneumophila subsp. pneumophila and Legionella pneumophila subsp. fraseri, were clearly separated genetically. In both rpoB and dotA trees, 79 Korean isolates used in this study constituted six clonal populations, four of which (designated subgroups P-I to P-IV) were...

  20. Separation of mandelic acid and its derivatives with new immobilized cellulose chiral stationary phase

    Institute of Scientific and Technical Information of China (English)

    Jie ZHOU; Qian LIU; Guang-jun FU; Zhen-zhong ZHANG

    2013-01-01

    A new liquid chromatographic method has been developed for the chiral separation of the enantiomers of mandelic acid and their derivatives 2-chloromandelic acid,4-hydroxymandelic acid,4-methoxymandelic acid,and 3,4,5-trismethoxymandelic acid.The enantiomers were separated by a CHIRALPAK(R) IC (250 mm×4.6 mm,5 μm).Mandelic acid,4-methoxymandelic acid,and 3,4,5-trismethoxymandelic acid were baseline resolved (resolution factor (Rs)=2.21,Rs=2.14,and Rs=3.70,respectively).In contrast,the enantioselectivities between CHIRALPAK(R) IC and 2-chloromandelic acid and 4-hydroxymandelic acid investigated were low.By comparing the chromatographs of mandelic acid enantiomers and mandelic acid spiked with (R)-mandelic acid,it was determined that the first effluent was (R)-mandelic acid.

  1. Radiochemical investigations of 177Lu-DOTA-8-Aoc-BBN[7-14]NH2: an in vitro/in vivo assessment of the targeting ability of this new radiopharmaceutical for PC-3 human prostate cancer cells

    International Nuclear Information System (INIS)

    Bombesin (BBN), a 14 amino acid peptide, is an analogue of human gastrin releasing peptide (GRP) that binds to GRP receptors (GRPr) with high affinity and specificity. The GRPr is over expressed on a variety of human cancer cells including prostate, breast, lung, and pancreatic cancers. The specific aim of this study was to identify a BBN analogue that can be radiolabeled with 177Lu and maintains high specificity for GRPr positive prostate cancer tumors in vivo. A preselected synthetic sequence via solid phase peptide synthesis (SPPS) was designed to produce a DOTA-BBN (DOTA 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) conjugate with the following general structure: DOTA-X-Q-W-A-V-G-H-L-M-(NH2), where the spacer group, X = ω-NH2(CH2)7COOH (8-Aoc). The BBN-construct was purified by reversed phase-HPLC (RP-HPLC). Electrospray Mass Spectrometry (ES-MS) was used to characterize both metallated and non-metallated BBN-conjugates. The new DOTA-conjugate was metallated with 177Lu(III)Cl3 or non-radioactive Lu(III)Cl3. The 177Lu(III)- and non-radiolabeled Lu(III)-conjugates exhibit the same retention times under identical RP-HPLC conditions. The 177Lu-DOTA-8-Aoc-BBN[7-14]NH2 conjugate was found to exhibit optimal pharmacokinetic properties in CF-1 normal mice. In vitro and in vivo models demonstrated the ability of the 177Lu-DOTA-8-Aoc-BBN[7-14]NH2 conjugate to specifically target GRP receptors expressed on PC-3 human prostate cancer cells

  2. Preclinical evaluation of [ 111 In]-DOTA-trastuzumab for clinical trials

    Directory of Open Access Journals (Sweden)

    Behrouz Alirezapour

    2014-01-01

    Full Text Available Context: Herceptin and its fragments have been radiolabeled and used in the imaging of human epidermal growth factor receptor 2 (HER2/neu-positive tumors and development of diagnostic kits is of great importance in radiopharmacy. Aims: In this study, 111 In-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-trastuzumab ( 111 In-DOTA-trastuzumab was successively prepared and evaluated for ultimate use in the HER2 antigen imaging in oncology. Settings and Design: The conjugate was prepared, labeled and evaluated using in vitro (radioimmunoassay [RIA], enzyme-linked immunosorbent assay (ELISA, stability, binding, internalization/in vivo (bio-distribution, single-photon emission computed tomography [SPECT] experiments. Materials and Methods: 111 In-DOTA-trastuzumab was prepared followed by determination of radiochemical purity (RCP, integrity of protein, immunoreactivity of radiolabeled antibody with HER2/neu antigen (by SkBr3 cell line binding and RIA methods were determined followed by stability tests, internalization studies and the tissue bio-distribution determination in wild-type rats as well as SPECT imaging in SkBr3-bearing mice. Statistical Analysis Used: All values were expressed as mean ± standard deviation (mean ± SD and the data were compared using Student′s t-test. Statistical significance was defined as P 95 ± 0.5%, S.A. 5.3 μCi/μg with the average number of chelators per antibody of 6:1 showing significant immune-reactivity retention using ELISA. In vitro stability was >90% in phosphate buffered saline and 80 ± 0.5% in serum over 48 h. Cell binding was significant (>0.79. In vitro internalization reached up to %12-13 in 10 h. Significant tumor uptake was observed. Conclusions: In vitro and in vivo/SPECT imaging in SkBr3-bearing mice demonstrated that 111 In-DOTA-trastuzumab is a potential compound for molecular imaging of SPECT for diagnosis and follow-up of HER2 expression in oncology.

  3. Pharmaceuticals and Surfactants from Alga-Derived Feedstock: Amidation of Fatty Acids and Their Derivatives with Amino Alcohols.

    Science.gov (United States)

    Tkacheva, Anastasia; Dosmagambetova, Inkar; Chapellier, Yann; Mäki-Arvela, Päivi; Hachemi, Imane; Savela, Risto; Leino, Reko; Viegas, Carolina; Kumar, Narendra; Eränen, Kari; Hemming, Jarl; Smeds, Annika; Murzin, Dmitry Yu

    2015-08-24

    Amidation of renewable feedstocks, such as fatty acids, esters, and Chlorella alga based biodiesel, was demonstrated with zeolites and mesoporous materials as catalysts and ethanolamine, alaninol, and leucinol. The last two can be derived from amino acids present in alga. The main products were fatty alkanol amides and the corresponding ester amines, as confirmed by NMR and IR spectroscopy. Thermal amidation of technical-grade oleic acid and stearic acid at 180 °C with ethanolamine were non-negligible; both gave 61% conversion. In the amidation of stearic acid with ethanolamine, the conversion over H-Beta-150 was 80% after 3 h, whereas only 63% conversion was achieved for oleic acid; this shows that a microporous catalyst is not suitable for this acid and exhibits a wrinkled conformation. The highest selectivity to stearoyl ethanolamide of 92% was achieved with mildly acidic H-MCM-41 at 70% conversion in 3 h at 180 °C. Highly acidic catalysts favored the formation of the ester amine, whereas the amide was obtained with a catalyst that exhibited an optimum acidity. The conversion levels achieved with different fatty acids in the range C12-C18 were similar; this shows that the fatty acid length does not affect the amidation rate. The amidation of methyl palmitate and biodiesel gave low conversions over an acidic catalyst, which suggested that the reaction mechanism in the amidation of esters was different. PMID:26197759

  4. An amine-derivatized, DOTA-loaded polymeric support for Fmoc Solid Phase Peptide Synthesis

    OpenAIRE

    Yoo, Byunghee; Sheth, Vipul R.; Pagel, Mark D.

    2009-01-01

    An amine-derivatized DOTA has been used to modify the surface of a polymeric support for conventional Solid Phase Peptide Synthesis (SPPS) following standard Fmoc chemistry methods. This methodology was used to synthesize a peptide-DOTA conjugate that was demonstrated to be a PARACEST MRI contrast agent. Therefore, this synthesis methodology can facilitate Fmoc SPPS of molecular imaging contrast agents.

  5. MR study of acute myocardial infarction with injection of Gd-DOTA (Fifteen patients)

    International Nuclear Information System (INIS)

    We studied 15 patients 4 to 8 days after myocardial infarction by using ECG gated MR before and after administration of 0.2 mmol/kg Gd-DOTA. The diagnosis in each patient was confirmed by electrocardiographic criteria, elevated levels of fractionated creatine kinase (CK) isoenzyme, thallium scintigraphy, ventriculography and coronarography. T1-weighted, spin-echo images, were obtained before and immediately after injection of Gd-DOTA and were repeated 15 min later. The site of infarction was visualized in 10 patients as an area of high signal intensity after the injection of Gd-DOTA. Contrast between normal and infarcted myocardium was greatest 15 min after injection. Three patients were excluded because of failure to acquire adequate MR studies. In 2 other patients the infarct was not detected. Before injection of Gd-DOTA, only 2 infarcts were detected. These results suggest that Gd-DOTA can improve MR visualization and detection of acute myocardial infarction

  6. Hyperpolarized 89Y NMR spectroscopic detection of yttrium ion and DOTA macrocyclic ligand complexation: pH dependence and Y-DOTA intermediates

    Science.gov (United States)

    Ferguson, Sarah; Kiswandhi, Andhika; Niedbalski, Peter; Parish, Christopher; Kovacs, Zoltan; Lumata, Lloyd

    Dissolution dynamic nuclear polarization (DNP) is a rapidly emerging physics technique used to enhance the signal strength in nuclear magnetic resonance (NMR) and imaging (MRI) experiments for nuclear spins such as yttrium-89 by >10,000-fold. One of the most common and stable MRI contrast agents used in the clinic is Gd-DOTA. In this work, we have investigated the binding of the yttrium and DOTA ligand as a model for complexation of Gd ion and DOTA ligand. The macrocyclic ligand DOTA is special because its complexation with lanthanide ions such as Gd3+ or Y3+ is highly pH dependent. Using this physics technology, we have tracked the complexation kinetics of hyperpolarized Y-triflate and DOTA ligand in real-time and detected the Y-DOTA intermediates. Different kinds of buffers were used (lactate, acetate, citrate, oxalate) and the pseudo-first order complexation kinetic calculations will be discussed. The authors would like to acknowledge the support by US Dept of Defense Award No. W81XWH-14-1-0048 and Robert A. Welch Foundation Grant No. AT-1877.

  7. Salicylic acid and some of its derivatives as antibacterial agents for viscose fabric.

    Science.gov (United States)

    Kantouch, A; El-Sayed, A Atef; Salama, M; El-Kheir, A Abou; Mowafi, S

    2013-11-01

    Salicylic acid and three of its derivatives were used to provide antibacterial properties to viscose fabrics. The four bactericides used were bonded to the viscose fabrics using epichlorohydrin or polymer binders. Optimization of the salicylic acid and its derivatives as well as the concentration of polymers was reported. The ability of the polymer binders to attract and bind the four bactericides was observed. The overall results show that the antibacterial reactivity of salicylic acid and its derivatives are in the following order 5-bromosalicylic acid>salicylic acid>5-chlorosalicylic acid>4-chlorosalicylic acid. Using epichlorohydrin as a binding agent, unfortunately, inhibits the bactericidal activity of the four bactericides. The FTIR study concludes that the reaction between salicylic acid as well as its derivatives with epichlorohydrin takes place through the phenolic group of the acids. The unexpected deterioration in the bactericidal properties of salicylic acid and its derivatives as a result of the treatment with epichlorohydrin could be due to the nature of interaction between the epichlorohydrin molecule and the acids molecules. PVP and PU show superior ability to sustain the four bactericides used even after 10 washing cycles.

  8. Hydroxyoctadecadienoic acids: Oxidised derivatives of linoleic acid and their role in inflammation associated with metabolic syndrome and cancer.

    Science.gov (United States)

    Vangaveti, Venkat N; Jansen, Holger; Kennedy, Richard Lee; Malabu, Usman H

    2016-08-15

    Linoleic acid (LA) is a major constituent of low-density lipoproteins. An essential fatty acid, LA is a polyunsaturated fatty acid, which is oxidised by endogenous enzymes and reactive oxygen species in the circulation. Increased levels of low-density lipoproteins coupled with oxidative stress and lack of antioxidants drive the oxidative processes. This results in synthesis of a range of oxidised derivatives, which play a vital role in regulation of inflammatory processes. The derivatives of LA include, hydroxyoctadecadienoic acids, oxo-​octadecadienoic acids, epoxy octadecadecenoic acid and epoxy-keto-octadecenoic acids. In this review, we examine the role of LA derivatives and their actions on regulation of inflammation relevant to metabolic processes associated with atherogenesis and cancer. The processes affected by LA derivatives include, alteration of airway smooth muscles and vascular wall, affecting sensitivity to pain, and regulating endogenous steroid hormones associated with metabolic syndrome. LA derivatives alter cell adhesion molecules, this initial step, is pivotal in regulating inflammatory processes involving transcription factor peroxisome proliferator-activated receptor pathways, thus, leading to alteration of metabolic processes. The derivatives are known to elicit pleiotropic effects that are either beneficial or detrimental in nature hence making it difficult to determine the exact role of these derivatives in the progress of an assumed target disorder. The key may lie in understanding the role of these derivatives at various stages of development of a disorder. Novel pharmacological approaches in altering the synthesis or introduction of synthesised LA derivatives could possibly help drive processes that could regulate inflammation in a beneficial manner. Chemical Compounds: Linoleic acid (PubChem CID: 5280450), 9- hydroxyoctadecadienoic acid (PubChem CID: 5312830), 13- hydroxyoctadecadienoic acid (PubChem CID: 6443013), 9-oxo

  9. Polyphosphorous acid catalyzed cyclization in the synthesis of cryptolepine derivatives

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    11-Oxo-10,11-dihydroxy-5H-indolo[3,2,b]quinoline7-carboxylic acid was obtained specifically by polyphosphorous acid catalyzed cyclization with optimal reaction conditions. Biological assays showed that it potentially inhibits the proteasomal chymotrypsin-like activity in vitro and suppresses breast cancer cell growth.

  10. Anacardic acid derived salicylates are inhibitors or activators of lipoxygenases

    NARCIS (Netherlands)

    Wisastra, Rosalina; Ghizzoni, Massimo; Boltjes, Andre; Haisma, Hidde J.; Dekker, Frank J.

    2012-01-01

    Lipoxygenases catalyze the oxidation of unsaturated fatty acids, such as linoleic acid, which play a crucial role in inflammatory responses. Selective inhibitors may provide a new therapeutic approach for inflammatory diseases. In this study, we describe the identification of a novel soybean lipoxyg

  11. Michael addition of thiols, carbon nucleophiles and amines to dehydroamino acid and dehydropeptide derivatives

    OpenAIRE

    Ferreira, Paula M.T.; Maia, Hernâni L. S.; Monteiro, Luís S.; Sacramento, Joana

    2001-01-01

    Michael additions of nitrogen heterocycles, thiols, carbon nucleophiles and amines to dehydroalanine derivatives, including a glycyldehydroalanine peptide, were performed in fair to good yields. Dehydroaminobutyric acid derivatives reacted only with the stronger nucleophiles but in considerably lower yields and often no reaction was observed with the corresponding dehydrophenylalanine derivatives. When a tosyl group was bonded to the nitrogen atom of the dehydroamino acid, in some cases the a...

  12. Preclinical study of radioiodinated glucose-Tyr3-octreotate: Comparison with 111In-DOTA-Tyr3-octreotate

    International Nuclear Information System (INIS)

    Full text: Targeted radionuclide imaging and treatment are based upon the interaction of radioligands with receptors in the target tissue (namely high density receptor specific tumours). As receptors for somatostatin (mainly somatostatin receptor subtype-2 /sstr2/) are over-expressed in several human tumours of endocrine origin, a number of radiolabeled somatostatin analogs have been recently introduced as the vectors for targeted imaging and therapy; commercially available 111In-DTPA-octreotide being a gold standard in this field. Several publications demonstrate that a substitution of Tyr instead of Phe in the peptide position 3 and oxidation of carboxyl end of octreotide significantly increased the affinity of the peptide to sstr2. More recently it has been shown that NH2-terminal carbohydration leads to a further improvement of the peptide receptor affinity and its retention in the tumour. In this study we present preclinical analysis of distribution profile and elimination pathways of radioiodinated glucose-Tyr3-octreotate (125I-gluc-TOCA) in comparison with that of another promising targeted radiopharmaceutical, namely 111In-DOTA-Tyr3-octreotate (111In- DOTA-TOCA). Gluc-TOCA was radioiodinated using chloramine-T method. For radiolabeling of DOTA-TOCA with radiometal, to 200 μl of 0.4 M acetate buffer with 0.24 M gentisic acid pH 5, 10μl of peptide solution in 0.1% TFA (1mg/ml) were added together with 0.5-1 mCi of 111InCl3 in 0.04 M HCl. Reaction mixture was heated 25 minutes to 90-95 deg. C. Pharmacokinetic studies were performed on male Wistar rats. Results confirmed that specific internalization of 125I-gluc-TOCA by sstr2 - expressing AR423 rat pancreatic carcinoma cells in vitro was about twice of that for 111In-DOTA-TOCA. In rats, 125I-gluc-TOCA exhibited prolonged plasma clearance in comparison with the other peptide. Slower decrease of plasma radioactivity after 125I-gluc-TOCA was due to its higher lipophilicity and thus higher plasma protein binding

  13. Production and applications of carbohydrate-derived sugar acids as generic biobased chemicals.

    Science.gov (United States)

    Mehtiö, Tuomas; Toivari, Mervi; Wiebe, Marilyn G; Harlin, Ali; Penttilä, Merja; Koivula, Anu

    2016-10-01

    This review considers the chemical and biotechnological synthesis of acids that are obtained by direct oxidation of mono- or oligosaccharide, referred to as sugar acids. It focuses on sugar acids which can be readily derived from plant biomass sources and their current and future applications. The three main classes of sugar acids are aldonic, aldaric and uronic acids. Interest in organic acids derived from sugars has recently increased, as part of the interest to develop biorefineries which produce not only biofuels, but also chemicals to replace those currently derived from petroleum. More than half of the most desirable biologically produced platform chemicals are organic acids. Currently, the only sugar acid with high commercial production is d-gluconic acid. However, other sugar acids such as d-glucaric and meso-galactaric acids are being produced at a lower scale. The sugar acids have application as sequestering agents and binders, corrosion inhibitors, biodegradable chelators for pharmaceuticals and pH regulators. There is also considerable interest in the use of these molecules in the production of synthetic polymers, including polyamides, polyesters and hydrogels. Further development of these sugar acids will lead to higher volume production of the appropriate sugar acids and will help support the next generation of biorefineries.

  14. The tumour sink effect on the biodistribution of {sup 68}Ga-DOTA-octreotate: implications for peptide receptor radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Beauregard, Jean-Mathieu [Peter MacCallum Cancer Centre and University of Melbourne, Centre for Cancer Imaging, Melbourne (Australia); Centre hospitalier universitaire de Quebec and Laval University, Molecular Imaging Research Group, Medical Imaging Department, Quebec City, QC (Canada); Hofman, Michael S.; Kong, Grace; Hicks, Rodney J. [Peter MacCallum Cancer Centre and University of Melbourne, Centre for Cancer Imaging, Melbourne (Australia)

    2012-01-15

    Tumour sequestration of radiotracer may lead to decreased bioavailability in healthy tissue resulting in lower absorbed radiation dose to critical organs. This study aims to assess the impact of disease burden, body habitus and urinary excretion on the biodistribution of {sup 68}Ga-DOTA-octreotate. Ten patients with highly varied burden of somatostatin receptor-positive neuroendocrine tumour on {sup 68}Ga-DOTA-octreotate positron emission tomography (PET)/CT were selected. Volumes of interest were drawn to derive the average uptake of renal parenchyma, spleen and body background, as well as to compute the fraction of injected activity sequestered in tumour and excreted in urine. Uptake values were assessed for correlation with tumour sequestration, weight, lean body weight, body surface area and urinary excretion. There was a trend for tumour sequestration, body habitus and urinary excretion to inversely influence all healthy tissue uptake values. In particular, renal uptake, splenic intensity and background soft tissue activity were all significantly correlated to composite factors combining tumour sequestration with body habitus and renal excretion. When combined with body habitus index or a body habitus index and renal excretion, tumour sequestration was strongly and significantly correlated inversely with renal uptake. Our results suggest that tumour sequestration of {sup 68}Ga-DOTA-octreotate is a major factor leading to a sink effect that decreases activity concentration in healthy organs such as the kidney. However, body habitus and renal function also influence tissue biodistribution, in a synergistic fashion. Compared with a fixed-dose peptide receptor radionuclide therapy protocol, an adjusted-dose regimen tailored to tumour burden, body habitus and renal function may allow greater radiation dose to individual lesions without substantially adding to toxicity in normal tissues. (orig.)

  15. A New β-Carboline Alkaloid and a New Derivate of Isoferulic Acid from Anemone altaica

    Institute of Scientific and Technical Information of China (English)

    Zhong Jie ZOU; Yue Sheng DONG; Jun Shan YANG

    2005-01-01

    A new β-carboline alkaloid, 4-(9H-β-carbolin-1-yl)-4-oxobutyric acid and a new derivate of isoferulic acid, (E)-3-(3-hydroxy-4-methoxyphenyl)acrylic acid carboxymethyl ester,were isolated from the roots of Anemone altaica. Their structures were determined on the basis of spectral data.

  16. Stability and interactions in mixed monolayers of fatty acid derivatives on artificial sea water

    NARCIS (Netherlands)

    Brzozowska, A.M.; Mugele, F.; Duits, M.H.G.

    2013-01-01

    We studied the formation and stability of fatty acid and derivatives films on aqueous sub-phases by means of Langmuir trough experiments. Films were prepared from pure stearic acid (SA), stearyl amine (SAm) and 12-phenyldodecanoic acid (PDA), and from binary systems of SA with either SAm or PDA. For

  17. Gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid conjugate of arabinogalactan as a potential liver-targeting magnetic resonance imaging contrast agent.

    Science.gov (United States)

    Xiao, Yan; Xue, Rong; You, Tianyan; Li, Xiaojing; Pei, Fengkui; Wang, Xuxia; Lei, Hao

    2014-08-18

    A novel biocompatible macromolecule (AG-CM-EDA-DOTA-Gd) was synthesized as a liver magnetic resonance imaging (MRI) contrast agent. AG-CM-EDA-DOTA-Gd consisted of a carboxymethyl-arabinogalactan unit conjugated with gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (Gd-DOTA) via ethylenediamine, and was specifically designed to bind to hepatocyte asialoglycoprotein in vivo, in an effort to develop a potential new tool for the diagnosis of liver diseases. The T1-relaxivity (8.87mmol(-1)Ls(-1)) of AG-CM-EDA-DOTA-Gd was 1.86 times than that of Gd-DOTA (4.76mmol(-1)Ls(-1)) in D2O at 9.4 T and 25°C. MRI experiments showed significant enhancement in rat liver following the intravenous administration of AG-CM-EDA-DOTA-Gd (0.094mmol Gd(3+)/kg body weight), which persisted for longer than Gd-DOTA (0.098mmol Gd(3+)/kg body weight). The mean percentage enhancements in the liver parenchyma were 85.2±6.5% and 19.3±3.3% for AG-CM-EDA-DOTA-Gd and Gd-DOTA, respectively. The results of this study therefore indicate that AG-CM-EDA-DOTA-Gd could be used as a potential liver-targeting contrast agent for MRI.

  18. Amifostine protects rat kidneys during peptide receptor radionuclide therapy with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Rolleman, Edgar J.; Forrer, Flavio; Bernard, Bert; Bijster, Magda; Valkema, Roelf; Krenning, Eric P.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Vermeij, Marcel [Erasmus MC, Department of Pathology, Rotterdam (Netherlands)

    2007-05-15

    In peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues, the kidneys are the major dose-limiting organs, because of tubular reabsorption and retention of radioactivity. Preventing renal uptake or toxicity will allow for higher tumour radiation doses. We tested the cytoprotective drug amifostine, which selectively protects healthy tissue during chemo- and radiotherapy, for its renoprotective capacities after PRRT with high-dose [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate. Male Lewis rats were injected with 278 or 555 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate to create renal damage and were followed up for 130 days. For renoprotection, rats received either amifostine or co-injection with lysine. Kidneys, blood and urine were collected for toxicity measurements. At 130 days after PRRT, a single-photon emission computed tomography (SPECT) scan was performed to quantify tubular uptake of {sup 99m}Tc-dimercaptosuccinic acid (DMSA), a measure of tubular function. Treatment with 555 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate resulted in body weight loss, elevated creatinine and proteinuria. Amifostine and lysine treatment significantly prevented this rise in creatinine and the level of proteinuria, but did not improve the histological damage. In contrast, after 278 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate, creatinine values were slightly, but not significantly, elevated compared with the control rats. Proteinuria and histological damage were different from controls and were significantly improved by amifostine treatment. Quantification of {sup 99m}Tc-DMSA SPECT scintigrams at 130 days after [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate therapy correlated well with 1/creatinine (r {sup 2} = 0.772, p < 0.001). Amifostine and lysine effectively decreased functional renal damage caused by high-dose [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate. Besides lysine, amifostine might be used in clinical PRRT as well

  19. Antiparasitic activity of prenylated benzoic acid derivatives from Piper species.

    Science.gov (United States)

    Flores, Ninoska; Jiménez, Ignacio A; Giménez, Alberto; Ruiz, Grace; Gutiérrez, David; Bourdy, Genevieve; Bazzocchi, Isabel L

    2009-03-01

    Fractionation of dichloromethane extracts from the leaves of Piper heterophyllum and P. aduncum afforded three prenylated hydroxybenzoic acids, 3-[(2E,6E,10E)-11-carboxy-3,7,15-trimethyl-2,6,10,14-hexadecatetraenyl)-4,5-dihydroxybenzoic acid, 3-[(2E,6E,10E)-11-carboxy-13-hydroxy-3,7,15-trimethyl-2,6,10,14-hexadecatetraenyl]-4,5-dihydroxybenzoic acid and 3-[(2E,6E,10E)-11-carboxy-14-hydroxy-3,7,15-trimethyl-2,6,10,15-hexadecatetraenyl]-4,5-dihydroxybenzoic acid, along with the known compounds, 4,5-dihydroxy-3-(E,E,E-11-formyl-3,7,15-trimethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid (arieianal), 3,4-dihydroxy-5-(E,E,E-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid, 4-hydroxy-3-(E,E,E-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid, 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-benzoic acid, 4-hydroxy-3-(3,7-dimethyl-2,6-octadienyl)benzoic acid and 4-hydroxy-3-(3-methyl-1-oxo-2-butenyl)-5-(3-methyl-2-butenyl)benzoic acid. Their structures were elucidated on the basis of spectroscopic data, including homo- and heteronuclear correlation NMR experiments (COSY, HSQC and HMBC) and comparison with data reported in the literature. Riguera ester reactions and optical rotation measurements established the compounds as racemates. The antiparasitic activity of the compounds were tested against three strains of Leishmania spp., Trypanosoma cruzi and Plasmodium falciparum. The results showed that 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-benzoic acid exhibited potent and selective activity against L. braziliensis (IC(50) 6.5 microg/ml), higher that pentamidine used as control. Moreover, 3-[(2E,6E,10E)-11-carboxy-3,7,15-trimethyl- 2,6,10,14-hexadecatetraenyl)-4,5-dihydroxybenzoic acid and 4-hydroxy-3-(3-methyl-1-oxo-2-butenyl)-5-(3-methyl-2-butenyl)benzoic acid showed moderate antiplasmodial (IC(50) 3.2 microg/ml) and trypanocidal (16.5 microg/ml) activities, respectively. PMID:19361822

  20. Endothelial Differentiation of Human Adipose-Derived Stem Cells on Polyglycolic Acid/Polylactic Acid Mesh.

    Science.gov (United States)

    Deng, Meng; Gu, Yunpeng; Liu, Zhenjun; Qi, Yue; Ma, Gui E; Kang, Ning

    2015-01-01

    Adipose-derived stem cell (ADSC) is considered as a cell source potentially useful for angiogenesis in tissue engineering and regenerative medicine. This study investigated the growth and endothelial differentiation of human ADSCs on polyglycolic acid/polylactic acid (PGA/PLA) mesh compared to 2D plastic. Cell adhesion, viability, and distribution of hADSCs on PGA/PLA mesh were observed by CM-Dil labeling, live/dead staining, and SEM examination while endothelial differentiation was evaluated by flow cytometry, Ac-LDL/UEA-1 uptake assay, immunofluorescence stainings, and gene expression analysis of endothelial related markers. Results showed hADSCs gained a mature endothelial phenotype with a positive ratio of 21.4 ± 3.7% for CD31+/CD34- when induced in 3D mesh after 21 days, which was further verified by the expressions of a comprehensive range of endothelial related markers, whereas hADSCs in 2D induced and 2D/3D noninduced groups all failed to differentiate into endothelial cells. Moreover, compared to 2D groups, the expression for α-SMA was markedly suppressed in 3D cultured hADSCs. This study first demonstrated the endothelial differentiation of hADSCs on the PGA/PLA mesh and pointed out the synergistic effect of PGA/PLA 3D culture and growth factors on the acquisition of mature characteristic endothelial phenotype. We believed this study would be the initial step towards the generation of prevascularized tissue engineered constructs.

  1. Pyrazine Carboxylic Acid Derivatives of Dichlorobis(Cyclopentadienyltitanium(IV

    Directory of Open Access Journals (Sweden)

    Satish Chandra Dixit

    2012-07-01

    Full Text Available Reactions of dichlorobis(cyclopentadienyltitanium(IV with pyrazine carboxylic acids viz. 2-pyrazine carboxylic acid (2-PzCH, 5-methyl-2-pyrazine carboxylic acid (MPzCH and 2,3-pyrazine dicarboxylic acid (2,3-PzDCH2 were carried out in different stoichiometric ratios. Complexes of the type Cp2Ti(2-PzCCl , Cp2Ti(2-PzC2 ,Cp2Ti(MPzCCl,Cp2Ti(MPzC2, Cp2Ti(2,3-PzDCHCl and Cp2Ti(2,3-PzDCH2 were obtained. These newly synthesized complexes were characterized on the basis of elemental analyses, electrical conductance, magnetic moment and spectral data.

  2. Pyrazine Carboxylic Acid Derivatives of Dichlorobis(Cyclopentadienyl)titanium(IV)

    OpenAIRE

    Satish Chandra Dixit; Rohit Kumar Singh

    2012-01-01

    Reactions of dichlorobis(cyclopentadienyl)titanium(IV) with pyrazine carboxylic acids viz. 2-pyrazine carboxylic acid (2-PzCH), 5-methyl-2-pyrazine carboxylic acid (MPzCH) and 2,3-pyrazine dicarboxylic acid (2,3-PzDCH2) were carried out in different stoichiometric ratios. Complexes of the type Cp2Ti(2-PzC)Cl , Cp2Ti(2-PzC)2 ,Cp2Ti(MPzC)Cl,Cp2Ti(MPzC)2, Cp2Ti(2,3-PzDCH)Cl and Cp2Ti(2,3-PzDCH)2 were obtained. These newly synthesized complexes were characterized on the basis of elemental analyse...

  3. Co2 chemosorption by functionalized amino acid derivatives

    DEFF Research Database (Denmark)

    2015-01-01

    The absorption and desorption behaviour of carbon dioxide (CO2) using a composition comprising an ionic compound comprising a cation [A+] and an anion [B-] is described, wherein the anion [B-] is a mono-amine functionalized amino acid.......The absorption and desorption behaviour of carbon dioxide (CO2) using a composition comprising an ionic compound comprising a cation [A+] and an anion [B-] is described, wherein the anion [B-] is a mono-amine functionalized amino acid....

  4. Chemical Synthesis of Uncommon Natural Bile Acids: The 9α-Hydroxy Derivatives of Chenodeoxycholic and Lithocholic Acids.

    Science.gov (United States)

    Iida, Takashi; Namegawa, Kazunari; Nakane, Naoya; Iida, Kyoko; Hofmann, Alan Frederick; Omura, Kaoru

    2016-09-01

    The chemical synthesis of the 9α-hydroxy derivatives of chenodeoxycholic and lithocholic acids is reported. For initiating the synthesis of the 9α-hydroxy derivative of chenodeoxycholic acid, cholic acid was used; for the synthesis of the 9α-hydroxy derivative of lithocholic acid, deoxycholic acid was used. The principal reactions involved were (1) decarbonylation of conjugated 12-oxo-Δ(9(11))-derivatives using in situ generated monochloroalane (AlH2Cl) prepared from LiAlH4 and AlCl3, (2) epoxidation of the deoxygenated Δ(9(11))-enes using m-chloroperbenzoic acid catalyzed by 4,4'-thiobis-(6-tert-butyl-3-methylphenol), (3) subsequent Markovnikov 9α-hydroxylation of the Δ(9(11))-enes with AlH2Cl, and (4) selective oxidation of the primary hydroxyl group at C-24 in the resulting 3α,9α,24-triol and 3α,7α,9α,24-tetrol to the corresponding C-24 carboxylic acids using sodium chlorite (NaClO2) in the presence of a catalytic amount of 2,2,6,6-tetramethylpiperidine 1-oxyl free radical (TEMPO) and sodium hypochlorite (NaOCl). The (1)H- and (13)C-NMR spectra are reported. The 3α,7α,9α-trihydroxy-5β-cholan-24-oic acid has been reported to be present in the bile of the Asian bear, and its 7-deoxy derivative is likely to be a bacterial metabolite. These bile acids are now available as authentic reference standards, permitting their identification in vertebrate bile acids. PMID:27319285

  5. Recent Advancements and Biological Activities of Aryl Propionic Acid Derivatives: (A Review

    Directory of Open Access Journals (Sweden)

    Harshita Dhall

    2016-08-01

    Full Text Available The aryl propionic acid derivatives belong to an important class of NSAIDs (Non Steroidal Anti-inflammatory Drugs. Ibuprofen, chemically called 2-(4-isobutyl phenyl propionic acid, is a well known NSAID. Aryl propionic acid derivatives possesses a wide range of biological activities including anti-bacterial, anti-convulsant, anti-cancer, analgesic and anti-inflammatory activities. Apart from very potent compounds in the field of analgesics and antipyrectics as Ibuprofen, Oxaprozin, Ketoprofen, Fenoprofen; aryl propionic acid derivatives plays important role to treat other ailments also. Through this review, an attempt has been made to emphasize on recent work done and recent advancements in arena of aryl propionic acid derivatives in view of medicinal chemistry.

  6. Development of novel radiogallium-labeled bone imaging agents using oligo-aspartic acid peptides as carriers.

    Directory of Open Access Journals (Sweden)

    Kazuma Ogawa

    Full Text Available (68Ga (T 1/2 = 68 min, a generator-produced nuclide has great potential as a radionuclide for clinical positron emission tomography (PET. Because poly-glutamic and poly-aspartic acids have high affinity for hydroxyapatite, to develop new bone targeting (68Ga-labeled bone imaging agents for PET, we used 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA as a chelating site and conjugated aspartic acid peptides of varying lengths. Subsequently, we compared Ga complexes, Ga-DOTA-(Aspn (n = 2, 5, 8, 11, or 14 with easy-to-handle (67Ga, with the previously described (67Ga-DOTA complex conjugated bisphosphonate, (67Ga-DOTA-Bn-SCN-HBP. After synthesizing DOTA-(Aspn by a Fmoc-based solid-phase method, complexes were formed with (67Ga, resulting in (67Ga-DOTA-(Aspn with a radiochemical purity of over 95% after HPLC purification. In hydroxyapatite binding assays, the binding rate of (67Ga-DOTA-(Aspn increased with the increase in the length of the conjugated aspartate peptide. Moreover, in biodistribution experiments, (67Ga-DOTA-(Asp8, (67Ga-DOTA-(Asp11, and (67Ga-DOTA-(Asp14 showed high accumulation in bone (10.5 ± 1.5, 15.1 ± 2.6, and 12.8 ± 1.7% ID/g, respectively but were barely observed in other tissues at 60 min after injection. Although bone accumulation of (67Ga-DOTA-(Aspn was lower than that of (67Ga-DOTA-Bn-SCN-HBP, blood clearance of (67Ga-DOTA-(Aspn was more rapid. Accordingly, the bone/blood ratios of (67Ga-DOTA-(Asp11 and (67Ga-DOTA-(Asp14 were comparable with those of (67Ga-DOTA-Bn-SCN-HBP. In conclusion, these data provide useful insights into the drug design of (68Ga-PET tracers for the diagnosis of bone disorders, such as bone metastases.

  7. Site-specific DOTA/europium-labeling of recombinant human relaxin-3 for receptor-ligand interaction studies.

    Science.gov (United States)

    Zhang, Wei-Jie; Luo, Xiao; Liu, Ya-Li; Shao, Xiao-Xia; Wade, John D; Bathgate, Ross A D; Guo, Zhan-Yun

    2012-08-01

    Relaxin-3 (also known as INSL7) is a recently identified neuropeptide belonging to the insulin/relaxin superfamily. It has putative roles in the regulation of stress responses, food intake, and reproduction by activation of its cognate G-protein-coupled receptor RXFP3. It also binds and activates the relaxin family peptide receptors RXFP1 and RXFP4 in vitro. To obtain a europium-labeled relaxin-3 as tracer for studying the interaction of these receptors with various ligands, in the present work we propose a novel site-specific labeling strategy for the recombinant human relaxin-3 that has been previously prepared in our laboratory. First, the N-terminal 6 × His-tag of the single-chain relaxin-3 precursor was removed by Aeromonas aminopeptidase and all of the primary amines of the resultant peptide were reversibly blocked by citroconic anhydride. Second, the A-chain N-terminus of the blocked peptide was released by endoproteinase Asp-N cleavage that removed the linker peptide between the B- and A-chains. Third, an alkyne moiety was introduced to the newly released A-chain N-terminus by reaction with the highly active primary amine-specific N-hydroxysuccinimide ester. Fourth, after removal of the reversible blockage under mild acidic condition, europium-loaded DOTA with an azide moiety was introduced to the two-chain relaxin-3 carrying the alkyne moiety through click chemistry. Using this site-specific labeling strategy, homogeneous monoeuropium-labeled human relaxin-3 could be obtained with good overall yield. In contrast, conventional random labeling resulted in a complex mixture that was poorly resolved because human relaxin-3 has four primary amine moieties that all react with the modification reagent. Both saturation and competition binding assays demonstrated that the DOTA/Eu(3+)-labeled relaxin-3 retained high binding affinity for human RXFP3, RXFP4, and RXFP1 and was therefore a suitable non-radioactive and stable tracer to study the interaction of various

  8. In vivo evaluation of a lead-labeled monoclonal antibody using the DOTA ligand

    International Nuclear Information System (INIS)

    The aim of this study was to assess the utility of a radioimmunoconjugate containing a lead radionuclide for therapy and scintigraphy applications. The radioimmunoconjugate evaluated consisted of a bifunctional DOTA ligand and monoclonal antibody (MAb) B72.3 using athymic mice bearing LS-174T tumors, human colon carcinoma xenografts. In the studies reported here, the lead-203-DOTA complex itself was first demonstrated to have in vivo stability. MAb B72.3 was then conjugated with the DOTA ligand and labeled with 203Pb, and the immunoreactivity of B72.3 was maintained. The localization of the radioimmunoconjugate to tumor tissue and other select organs paralleled that of DOTA-125I-B72.3, suggesting a similar metabolic pattern of the two radioimmunoconjugates. Thus, the DOTA-metal complex does not alter the behavior of the radioimmunoconjugate. Tumor localization of the 203Pb-DOTA-B72.3 conjugate was demonstrated with biodistribution studies as well as immunoscintigraphy studies. Such data highlight the stability of a lead radionuclide in the DOTA ligand. The suitability of this chelation chemistry for labeling radioimmunoconjugates with a lead radionuclide now makes its application in nuclear medicine a feasible proposition. (orig.)

  9. Labelling of the peptide Dota-Octreotate with Lutetium 177

    International Nuclear Information System (INIS)

    In this work is described the optimization of the reaction conditions to obtain the complex 177 Lu-Dota-TATE with a radiochemical purity > 95%, even so the studies of stability In vitro to the dilution in saline solution, stability in human serum and challenge to the cystein. The biodistribution studies are presented in mice Balb-C and the tests of biological recognition using one lines cellular of pancreatic adenoma (AR42-J). The obtained results show a high stability of the radio complex in vitro, since it doesn't suffer trans chelation from the Lutetium-177 to plasmatic proteins. The biodistribution tests in mice Balb-C demonstrated an appropriate lipophilly of the complex to be excreted in more proportion by the kidneys without significant accumulation in healthy tissues. It is necessary to mention that the drop activity specifies (3.54 μg / 37 MBq) obtained in the irradiation of 176 Lu2O3 it allowed to verify the union of the 177Lu-Dota-Tate to membrane receivers but without being able to obtain the saturation curves and competition required to characterize quantitatively the biological recognition. (Author)

  10. Synthesis of Tetrahydrofuran and Tetrahydropyran Derivatives Catalyzed by Tungstophosphoric Acid in Ionic Liquid

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Synthesis of tetrahydrofuran and tetrahydropyran derivatives catalyzed by tungstophosphoric acid (H3PW12O4o) were conveniently performed with high yield from the corresponding unsaturated alcohols in ionic liquid. Sufuric acid (H2SO4), trifluoromathanesulfonic acid (TfOH)and p-toluenesulfonic acid (TsOH) were also explored for preparing these products in ionic liquid.The catalysts and ionic liquid can be easily recovered and reused.

  11. Azorhodanine derivatives as inhibitors for acidic corrosion of nickel.

    Science.gov (United States)

    Fouda, Abd El-Aziz S; Al-Sarawy, Ahmed A; Omar, Tark M

    2005-01-01

    Azorhodanine derivatives (HL1-HL5) were tested as corrosion inhibitors for nickel in 2M HNO3 solution using weight loss and galvanostatic polarization techniques. The results showed that these derivatives act as inhibitors for nickel in this medium. The inhibition was assumed to occur via adsorption of the inhibitor molecule on the metal surface. Polarization measurements indicated that these compounds act as mixed-type inhibitors, but the cathode is more polarized when an external current was applied. This means that these compounds retard the rate of hydrogen evolution and the rate of dissolution of the metal. Results showed that azorhodanine derivatives are adsorbed on the nickel surface following Temkin's adsorption isotherm. The activation energy and thermodynamic parameters were calculated and discussed at different temperatures (30-45 degrees C).

  12. [{sup 177}Lu]DOTA-anti-CD20: Labeling and pre-clinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Audicio, Paola F., E-mail: paudicio@cin.edu.u [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay); Castellano, Gustavo, E-mail: gcas@famaf.unc.edu.a [FaMAF, Universidad Nacional de Cordoba, Ciudad Universitaria, 5016 Cordoba (Argentina); Tassano, Marcos R.; Rezzano, Maria E.; Fernandez, Marcelo [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay); Riva, Eloisa [Clinica Hematologica ' Prof. Dra. L. Diaz' , Hospital de Clinicas. Av. Italia. sn, Montevideo (Uruguay); Robles, Ana; Cabral, Pablo; Balter, Henia; Oliver, Patricia [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay)

    2011-07-15

    Anti-CD20 (Rituximab), a specific chimeric monoclonal antibody used in CD20-positive Non-Hodgkin's Lymphoma, was conjugated to a bifunctional quelate (DOTA) and radiolabeled with {sup 177}Lu through a simple method. [{sup 177}Lu]-DOTA-anti-CD20 was obtained with a radiochemical purity higher than 97%, and showed good chemical and biological stability, maintaining its biospecificity to CD20 antigens. Monte Carlo simulation showed high doses deposited on a spheroid tumor mass model. This method seems to be an appropriate alternative for the production of [{sup 177}Lu]-DOTA-anti-CD20 as therapeutic radiopharmaceutical.

  13. Pseudoephedrine-Directed Asymmetric α-Arylation of α-Amino Acid Derivatives.

    Science.gov (United States)

    Atkinson, Rachel C; Fernández-Nieto, Fernando; Mas Roselló, Josep; Clayden, Jonathan

    2015-07-27

    Available α-amino acids undergo arylation at their α position in an enantioselective manner on treatment with base of N'-aryl urea derivatives ligated to pseudoephedrine as a chiral auxiliary. In situ silylation and enolization induces diastereoselective migration of the N'-aryl group to the α position of the amino acid, followed by ring closure to a hydantoin with concomitant explulsion of the recyclable auxiliary. The hydrolysis of the hydantoin products provides derivatives of quaternary amino acids. The arylation avoids the use of heavy-metal additives, and is successful with a range of amino acids and with aryl rings of varying electronic character.

  14. Endothelial Differentiation of Human Adipose-Derived Stem Cells on Polyglycolic Acid/Polylactic Acid Mesh

    Directory of Open Access Journals (Sweden)

    Meng Deng

    2015-01-01

    Full Text Available Adipose-derived stem cell (ADSC is considered as a cell source potentially useful for angiogenesis in tissue engineering and regenerative medicine. This study investigated the growth and endothelial differentiation of human ADSCs on polyglycolic acid/polylactic acid (PGA/PLA mesh compared to 2D plastic. Cell adhesion, viability, and distribution of hADSCs on PGA/PLA mesh were observed by CM-Dil labeling, live/dead staining, and SEM examination while endothelial differentiation was evaluated by flow cytometry, Ac-LDL/UEA-1 uptake assay, immunofluorescence stainings, and gene expression analysis of endothelial related markers. Results showed hADSCs gained a mature endothelial phenotype with a positive ratio of 21.4 ± 3.7% for CD31+/CD34− when induced in 3D mesh after 21 days, which was further verified by the expressions of a comprehensive range of endothelial related markers, whereas hADSCs in 2D induced and 2D/3D noninduced groups all failed to differentiate into endothelial cells. Moreover, compared to 2D groups, the expression for α-SMA was markedly suppressed in 3D cultured hADSCs. This study first demonstrated the endothelial differentiation of hADSCs on the PGA/PLA mesh and pointed out the synergistic effect of PGA/PLA 3D culture and growth factors on the acquisition of mature characteristic endothelial phenotype. We believed this study would be the initial step towards the generation of prevascularized tissue engineered constructs.

  15. Labelling of the peptide Dota-Octreotate with Lutetium 177; Marcado del peptido Dota-Octreotate con Lutecio 177

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez B, C.A

    2004-07-01

    In this work is described the optimization of the reaction conditions to obtain the complex {sup 177} Lu-Dota-TATE with a radiochemical purity > 95%, even so the studies of stability In vitro to the dilution in saline solution, stability in human serum and challenge to the cystein. The biodistribution studies are presented in mice Balb-C and the tests of biological recognition using one lines cellular of pancreatic adenoma (AR42-J). The obtained results show a high stability of the radio complex in vitro, since it doesn't suffer trans chelation from the Lutetium-177 to plasmatic proteins. The biodistribution tests in mice Balb-C demonstrated an appropriate lipophilly of the complex to be excreted in more proportion by the kidneys without significant accumulation in healthy tissues. It is necessary to mention that the drop activity specifies (3.54 {mu}g / 37 MBq) obtained in the irradiation of {sup 176} Lu{sub 2}O{sub 3} it allowed to verify the union of the {sup 177}Lu-Dota-Tate to membrane receivers but without being able to obtain the saturation curves and competition required to characterize quantitatively the biological recognition. (Author)

  16. In vitro Evaluation of a Bombesin Antagonistic Analogue Conjugated with DOTA-Ala(SO{sub 3}H)-Aminooctanoyl for Targeting of the Gastrin-releasing Peptide Receptor

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jae Cheong; Cho, Eun Ha; Kim, Jin Joo; Lee, So Young; Choi, Sang Mu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    As Bombesin (BBS) binds with high affinity to GRPR, BBS derivatives have been labeled with various radionuclides such as {sup 99}mTc, {sup 111}In, {sup 90}Y, {sup 64}Cu, {sup 177}Lu, {sup 68}Ga, or {sup 18}F and have proved to be successful candidates for peptide receptor radiotherapy (PRRT). In this study, we employed Ala(SO{sub 3}H)-Aminooctanoyl as a linker of BBS antagonistic peptide sequence, Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH{sub 2}, with DOTA to prepare radiolabeled candidates for GRPR targeting. A DOTA-conjugated BBS antagonistic analogue was synthesized and radiolabeled with {sup 177}Lu, and in vitro characteristics on GRPR-overexpressing human prostate tumor cells were evaluated. In conclusion, a novel BBS antagonistic analogue, {sup 177}Lu-DOTA-sBBNA, is a promising candidate for the targeting of GRPR-over-expressing tumors. Further investigations to evaluate its in vivo characteristics and therapeutic efficacy are needed.

  17. 177Lu-DOTA-HH1, a novel anti-CD37 radio-immunoconjugate: a study of toxicity in nude mice.

    Directory of Open Access Journals (Sweden)

    Ada H V Repetto-Llamazares

    Full Text Available CD37 is an internalizing B-cell antigen expressed on Non-Hodgkin lymphoma (NHL and chronic lymphocytic leukemia cells (CLL. The anti-CD37 monoclonal antibody HH1 was conjugated to the bifunctional chelator p-SCN-Bn-DOTA and labelled with the beta-particle emitting radionuclide 177Lu creating the radio-immunoconjugate (RIC 177Lu-DOTA-HH1 (177Lu-HH1, trade name Betalutin. The present toxicity study was performed prior to initiation of clinical studies with 177Lu-HH1.Nude mice with or without tumor xenografts were treated with 50 to 1000 MBq/kg 177Lu- HH1 and followed for clinical signs of toxicity up to ten months. Acute, life threatening bone marrow toxicity was observed in animals receiving 800 and 1000 MBq/kg 177Lu-HH1. Significant changes in serum concentrations of liver enzymes were evident for treatment with 1000 MBq/kg 177Lu-HH1. Lymphoid depletion, liver necrosis and atrophy, and interstitial cell hyperplasia of the ovaries were also observed for mice in this dose group.177Lu-DOTA-HH1 was well tolerated at dosages about 10 times above those considered relevant for radioimmunotherapy in patients with B-cell derived malignancies.The toxicity profile was as expected for RICs. Our experimental results have paved the way for clinical evaluation of 177Lu-HH1 in NHL patients.

  18. Formation of Amino Acid Derived Cheese Flavour Compounds

    NARCIS (Netherlands)

    Smit, B.A.

    2004-01-01

    Lactic acid bacteria (LAB), among them Lactococcus lactis, are often used for the fermentation of milk into various products, such as cheeses. For their growth and maintenance LAB metabolise milk sugar, protein and fat into various low molecular compounds, which sometimes have strong flavour charact

  19. Phenolic acid metabolites as biomarkers for tea- and coffee-derived polyphenol exposure in human subjects.

    Science.gov (United States)

    Hodgson, Jonathan M; Chan, Shin Yee; Puddey, Ian B; Devine, Amanda; Wattanapenpaiboon, Naiyana; Wahlqvist, Mark L; Lukito, Widjaja; Burke, Valerie; Ward, Natalie C; Prince, Richard L; Croft, Kevin D

    2004-02-01

    Tea and coffee are rich in polyphenols with a variety of biological activities. Many of the demonstrated activities are consistent with favourable effects on the risk of chronic diseases. 4-O-methylgallic acid (4OMGA) and isoferulic acid are potential biomarkers of exposure to polyphenols derived from tea and coffee respectively. 4OMGA is derived from gallic acid in tea, and isoferulic acid is derived from chlorogenic acid in coffee. Our major objective was to explore the relationships of tea and coffee intake with 24 h urinary excretion of 4OMGA and isoferulic acid in human subjects. The relationships of long-term usual (111 participants) and contemporaneously recorded current (344 participants) tea and coffee intake with 24 h urinary excretion of 4OMGA and isoferulic acid were assessed in two populations. 4OMGA was related to usual (r 0.50, Pcoffee intake. Overall, our present results are consistent with the proposal that 4OMGA is a good biomarker for black tea-derived polyphenol exposure, but isoferulic acid may be of limited usefulness as a biomarker for coffee-derived polyphenol exposure.

  20. Syntheses,characteristics,and fluorescence properties of complexes of europium with benzoic acid and its derivatives

    Institute of Scientific and Technical Information of China (English)

    ZHOU Zhongcheng; SHU Wangen; RUAN Jianming; HUANG Boyun; LIU Younian

    2004-01-01

    The binary complexes of europium with benzoic acid and its derivatives (phthalic acid, m-phthalic acid,o-aminobenzoic acid, salicylic acid, and sulfosalicylic acid) were synthesized and their compositions were identified by elemental analyses. UV and IR of the complexes have been investigated. The UV spectra indicated that the complexes' ultraviolet absorption were mainly the ligands' absorption. The IR spectra showed that the IR spectra of complexes are different from those of free ligands. The fluorescence properties of them were investigated by using luminescence spectroscopy, the results showed that only three complexes appear as better luminescence, they were Eu-benzoic acid,Eu-m-phthalic acid and Eu-phthalic acid, while the others exhibited the ligands' wideband emission.

  1. Formation of Amino Acid Derived Cheese Flavour Compounds

    OpenAIRE

    Smit, B.A.

    2004-01-01

    Lactic acid bacteria (LAB), among them Lactococcus lactis, are often used for the fermentation of milk into various products, such as cheeses. For their growth and maintenance LAB metabolise milk sugar, protein and fat into various low molecular compounds, which sometimes have strong flavour characteristics. This thesis focuses on the production of one class of these compounds as a model system: aldehydes, in particular the key-flavour compounds 3-methylbutanal and 2-methyl propanal, which ar...

  2. Silica with immobilized phosphinic acid-derivative for uranium extraction.

    Science.gov (United States)

    Budnyak, Tetyana M; Strizhak, Alexander V; Gładysz-Płaska, Agnieszka; Sternik, Dariusz; Komarov, Igor V; Kołodyńska, Dorota; Majdan, Marek; Tertykh, Valentin А

    2016-08-15

    A novel adsorbent benzoimidazol-2-yl-phenylphosphinic acid/aminosilica adsorbent (BImPhP(O)(OH)/SiO2NH2) was prepared by carbonyldiimidazole-mediated coupling of aminosilica with 1-carboxymethylbenzoimidazol-2-yl-phenylphosphinic acid. It was obtained through direct phosphorylation of 1-cyanomethylbenzoimidazole by phenylphosphonic dichloride followed by basic hydrolysis of the nitrile. The obtained sorbent was well characterized by physicochemical methods, such as differential scanning calorimetry-mass spectrometry (DSC-MS), surface area and pore distribution analysis (ASAP), scanning electron microscopy (SEM), X-ray photoelectron (XPS) and Fourier transform infrared (FTIR) spectroscopies. The adsorption behavior of the sorbent and initial silica gel as well as aminosilica gel with respect to uranium(VI) from the aqueous media has been studied under varying operating conditions of pH, concentration of uranium(VI), contact time, and desorption in different media. The synthesized material was found to show an increase in adsorption activity with respect to uranyl ions in comparison with the initial compounds. In particular, the highest adsorption capacity for the obtained modified silica was found at the neutral pH, where one gram of the adsorbent can extract 176mg of uranium. Under the same conditions the aminosilica extracts 166mg/g, and the silica - 144mg/g of uranium. In the acidic medium, which is common for uranium nuclear wastes, the synthesized adsorbent extracts 27mg/g, the aminosilica - 16mg/g, and the silica - 14mg/g of uranium. It was found that 15% of uranium ions leached from the prepared material in acidic solutions, while 4% of uranium can be removed in a phosphate solution. PMID:27177215

  3. Radiolabelled of c-DOTA-RGD and c-DOTA-RGDf with 177Lu and evaluation in vitro and in vivo stability

    International Nuclear Information System (INIS)

    Integrin αvβ3 has a critical role in tumor angio genesis and metastasis. Radiolabelled peptides based on the Arg-Gly-Asp (RGD) sequence have been reported as radiopharmaceuticals with high affinity and selectivity for the αvβ3 integrin. The aim of this study was to label c-DOTA-RGD and c-DOTA-RGDf peptides with 177Lu and to evaluate their in vitro and in vivo stability as potential specific therapeutic radiopharmaceuticals. Labelled was carried out by direct reaction of 177LuCl3 with c-DOTA-RGD peptides in 1 M acetate buffer ph 5.5 at 90o C for 30 min. Radiochemical purity and stability studies were realized by reversed phase HPLC and I TLC-Sg analyses in human serum and saline solution. Biological recognition was performed using MCF7 tumor cells (positive αvβ3) and in athymic mice with induced MCF7 tumors. Molecular mechanics and quantum mechanics calculations were performed to explain experimental results associated with the molecular recognition. 177Lu-DOTA-RGD and 177Lu-DOTA-RGDf were obtained with radiochemical purities > 95%, showing adequate in vitro and in vivo stability and specific binding to □v□3 receptors. (Author)

  4. Palladium-Catalyzed C–C Bond Formations via Activation of Carboxylic Acids and Their Derivatives

    OpenAIRE

    Song, Bingrui

    2013-01-01

    Applications of carboxylic acids and their derivatives in transition metal-catalyzed cross-coupling reactions regio-selectively forming Csp3-Csp2, and Csp2-Csp2 bonds were explored in this thesis. Several important organic building blocks such as aryl acetates, diaryl acetates, imines, ketones, biaryls, styrenes and polysubstituted alkenes were successfully accessed from carboxylic acids and their derivatives by the means of C–H activation and decarboxylative cross-couplings. An efficient ...

  5. Antitrypanosomal Activity of Novel Benzaldehyde-Thiosemicarbazone Derivatives from Kaurenoic Acid

    OpenAIRE

    2011-01-01

    A series of new thiosemicarbazones derived from natural diterpene kaurenoic acid were synthesized and tested against the epimastigote forms of Trypanosoma cruzi to evaluate their antitrypanosomal potential. Seven of the synthesized thiosemicarbazones were more active than kaurenoic acid with IC50 values between 2-24.0 mM. The o-nitro-benzaldehyde-thiosemicarbazone derivative was the most active compound with IC50 of 2.0 mM. The results show that the structural modifications accomplished enhan...

  6. Structure–anticancer activity relationships among 4-azolidinone-3-carboxylic acids derivatives

    OpenAIRE

    Lesyk R. B.; Kaminskyy D. V.

    2010-01-01

    The aim of present research was investigation of anticancer activity of 4-azolidinone-3-carboxylic acids derivatives, and studies of structure–activity relationships (SAR) aspects. Methods. Organic synthesis; spectral methods; anticancer screening was performed according to the US NCI protocol (Developmental Therapeutic Program). Results. The data of new 4-thiazolidinone-3-alkanecarboxylic acids derivatives in vitro anticancer activity were described. The most active compounds which belong to...

  7. Anti-inflammatory pro-resolving derivatives of omega-3 and omega-6 polyunsaturated fatty acids

    OpenAIRE

    Jerzy Z. Nowak

    2010-01-01

    Inflammation is a physiological defense reaction of living tissues to injury or infection. An array of mediators, including those derived from omega-6 (ω6) polyunsaturated fatty acids (PUFAs), such as arachidonic acid (AA) e.g. prostaglandins and leukotrienes, promote the inflammatory response. Acute inflammation has several programmed fates, including complete resolution or progression to chronic inflammation, scarring, and eventual loss of tissue function. Studies on AA-derived proinflammat...

  8. MR Diagnosis of a Pulmonary Embolism: Comparison of P792 and Gd-DOTA for First-Pass Perfusion MRI and Contrast-Enhanced 3D MRA in a Rabbit Model

    Energy Technology Data Exchange (ETDEWEB)

    Keilholz, Shella D. [Emory University and Georgia Institute of Technology, Atlanta (United States); Bozlar, Ugur; Fujiwara, Naomi; Mata, Jaime F.; Berr, Stuart S.; Hagspiel, Klaus D. [Gulhane Military Medical Academy, Ankara (Turkmenistan); Corot, Claire [Guerbet Research, Aulnay-sous-Bois (France)

    2009-10-15

    To compare P792 (gadomelitol, a rapid clearance blood pool MR contrast agent) with gadolinium-tetraazacyclododecanetetraacetic acid (Gd- DOTA), a standard extracellular agent, for their suitability to diagnose a pulmonary embolism (PE) during a first-pass perfusion MRI and 3D contrastenhanced (CE) MR angiography (MRA). A perfusion MRI or CE-MRA was performed in a rabbit PE model following the intravenous injection of a single dose of contrast agent. The time course of the pulmonary vascular and parenchymal enhancement was assessed by measuring the signal in the aorta, pulmonary artery, and lung parenchyma as a function of time to determine whether there is a significant difference between the techniques. CE-MRA studies were evaluated by their ability to depict the pulmonary vasculature and following defects between 3 seconds and 15 minutes after a triple dose intravenous injection of the contrast agents. The P792 and Gd-DOTA were equivalent in their ability to demonstrate PE as perfusion defects on first pass imaging. The signal from P792 was significantly higher in vasculature than that from Gd-DOTA between the first and the tenth minutes after injection. The results suggest that a CE-MRA PE could be reliably diagnosed up to 15 minutes after injection. P792 is superior to Gd-DOTA for the MR diagnosis of PE.

  9. MR imaging experimental study of intraarticular kinetics of Gd-DOTA

    International Nuclear Information System (INIS)

    This paper evaluates the intraarticular kinetics of a paramagnetic MR contrast agent. Imaging parameters and concentration of Gd-DOTA (Guerbet, France) were initially determined by in vitro imaging measurements performed with a 1.5-T magnet. Ten glass tubes of varying concentrations of diluted Gd-DOTA were imaged with different TRs. To optimize the signal intensity differences, the TR was 220 msec with a concentration of 2 mmol/L, 300 mOsm/kg corresponding to the highest signal intensity. Intraarticular injection of 0.8 mL of a 2-mmol/L solution of Gd-DOTA was performed in four Beagle dogs. Sagittal images of the knees were obtained after injection (TR, 220 msec; TE, 20 msec). Measurements of the signal intensity of the joint space were obtained every 5 minutes and validated with two tubes containing water and Gd-DOTA solution (2 mmol/L)

  10. An Efficient Solid Acid Promoted Synthesis of Quinoxaline Derivatives at Room Temperature

    Institute of Scientific and Technical Information of China (English)

    AHMAD,Shaabani; ALI,Maleki

    2007-01-01

    Quinoxaline derivatives have been synthesized in a very short time with excellent yields by the condensation of 1,2-diamines with aliphatic or aromatic 1,2-dicarbonyl compounds or benzilmonoxime in the presence of silica sul-furic acid as a very inexpensive solid acid catalyst at room temperature. The recovery and reuse of the catalyst are also satisfactory.

  11. Cellular fatty acid composition of marine-derived fungi

    Digital Repository Service at National Institute of Oceanography (India)

    PrabhaDevi; Shridhar, M.P.D.; DeSouza, L.; Naik, C.G.

    -1269. 13 Barclay, W.R., Meager, K.M. & Abril, J.R., Heterotrophic production of long chain omega-3 fatty acids utilizing algae and algae like microorganisms, J. Appl. Phycol., 6(1994) 123-129. 14 Ratledge, C., Microorganisms as sources... with the recognition that certain strains and species of both yeast and filamentous fungi are capable of producing relatively high amounts of fats and oils. There is also particular interest in specific fungal lipid products, such as those having biological...

  12. Synthesis and anti-tumor activity of all-trans retinoic acid derivatives

    Institute of Scientific and Technical Information of China (English)

    Juan Shen; Jing Bo Shi; Fei Hu Chen; Yuan Wang; Jing Jing Ruan; Yua Huang

    2009-01-01

    A series of retinoate and retinamide derivatives were designed, synthesized, and their anti-tumor activities were investigated in NB4 by MTT and flow cytometry assays (FCM). All compounds showed cytotoxicity, especially compounds 1a and 1d exhibited a higher cytotoxicity than other derivatives and all-traus retinoic acid (ATRA). Furthermore, compound ld could induce NB4 cell lines differentiation efficiently.

  13. p-Nitrobenzoic acid promoted synthesis of 1,5-benzodiazepine derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Varala, Ravi; Enugala, Ramu; Adapa, Srinivas R. [Indian Institute of Chemical Technology, Hyderabad (India)]. E-mail: rvarala_iict@yahoo.co.in

    2007-03-15

    p-Nitrobenzoic acid was found to be the versatile Bronsted organic acid promoter among the carboxylic acids tested for the preparation of 1,5-benzodiazepine derivatives from a wide range of substituted o-phenylenediamines and ketones. The corresponding products were obtained in good isolated yields (62-92%) under mild conditions using acetonitrile as solvent at ambient temperature. Further, the reagent could be easily recovered and reused. (author00.

  14. Green Synthesis and Urease Inhibitory Activity of Spiro-Pyrimidinethiones/Spiro-Pyrimidinones-Barbituric Acid Derivatives

    OpenAIRE

    Mohammadi Ziarani, Ghodsi; Asadi, Shima; Faramarzi, Sakineh; Amanlou, Massoud

    2015-01-01

    Sulfonic acid functionalized SBA-15 (SBA-Pr-SO3H) with pore size 6 nm as an efficient heterogeneous nanoporous solid acid catalyst exhibited good catalytic activity in the Biginelli-like reaction in the synthesis of spiroheterobicyclic rings with good yield and good recyclability. Spiro-pyrimidinethiones/spiro-pyrimidinones-barbituric acid derivatives were synthesized in a simple and efficient method using the one-pot three-component reaction of a cyclic 1,3- dicarbonyl compounds (barbituric ...

  15. Acyl Meldrum's acid derivatives: application in organic synthesis

    International Nuclear Information System (INIS)

    This review is focused on an important class of Meldrum's acid derivatives commonly known as acyl Meldrum's acids. The preparation methods of these compounds are considered including the recently proposed and rather rarely used ones. The chemical properties of acyl Meldrum's acids are described in detail, including thermal stability and reactions with various nucleophiles. The possible mechanisms of these transformations are analyzed. The bibliography includes 134 references

  16. Two New Cholic Acid Derivatives from the Marine Ascidian-Associated Bacterium Hasllibacter halocynthiae

    Directory of Open Access Journals (Sweden)

    Sung Hun Kim

    2012-10-01

    Full Text Available The investigation of secondary metabolites in liquid cultures of a recently discovered marine bacterium, Hasllibacter halocynthiae strain KME 002T, led to the isolation of two new cholic acid derivatives. The structures of these compounds were determined to be 3,3,12-trihydroxy-7-ketocholanic acid (1 and 3,3,12-trihydroxy-7-deoxycholanic acid (2 through HRFABMS and NMR data analyses.

  17. Modification of oligo-Ricinoleic Acid and Its Derivatives with 10-Undecenoic Acid via Lipase-Catalyzed Esterification

    Directory of Open Access Journals (Sweden)

    M. Claudia Montiel

    2012-04-01

    Full Text Available Lipases were employed under solvent-free conditions to conjugate oligo-ricinoleic acid derivatives with 10-undecenoic acid, to incorporate a reactive terminal double bond into the resultant product. First, undecenoic acid was covalently attached to oligo-ricinoleic acid using immobilized Candida antarctica lipase (CAL at a 30% yield. Thirty percent conversion also occurred for CAL-catalyzed esterification between undecenoic acid and biocatalytically-prepared polyglycerol polyricinoleate (PGPR, with attachment of undecenoic acid occurring primarily at free hydroxyls of the polyglycerol moiety. The synthesis of oligo-ricinoleyl-, undecenoyl- structured triacylglycerols comprised two steps. The first step, the 1,3-selective lipase-catalyzed interesterification of castor oil with undecenoic acid, occurred successfully. The second step, the CAL-catalyzed reaction between ricinoleyl-, undecenoyl structured TAG and ricinoleic acid, yielded approximately 10% of the desired structured triacylglycerols (TAG; however, a significant portion of the ricinoleic acid underwent self-polymerization as a side-reaction. The employment of gel permeation chromatography, normal phase HPLC, NMR, and acid value measurements was effective for characterizing the reaction pathways and products that formed.

  18. Radiolabeling parameters of {sup 177}Lu-DOTA-RITUXIMAB

    Energy Technology Data Exchange (ETDEWEB)

    Massicano, Adriana V.F.; Alcarde, Lais F.; Oliveira, Ricardo S.; Mengatti, Jair; Araujo, Elaine B. de, E-mail: adriana.avfernandes@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Cancer treatment using radioimmunotherapy (RIT) has been the focus of much research in the last two decades. In RIT, a radioisotope is coupled to a monoclonal antibody (mAb) to form a tumor-specific target agent to improve the cytocidal effect of the mAbs. RIT allows the systemic delivery of radiation to disease target by mAbs while sparing normal tissues. Rituximab® (Mabthera - Roche) is a chimeric mouse-human monoclonal antibody; it selectively binds with high affinity to the CD20 antigen, a hydrophobic transmembrane protein, which is expressed on B-lymphocytes and in more than 90% of B cell non-Hodgkin's lymphomas (NHL). The conjugation and radiolabeling process involve special conditions of pH and temperature, long processes of manipulation and mixing. All this process can damage the antibody structure and compromise its clinical application. Therefore, these parameters must be largely studied. The aim of this work was to evaluate the best radiolabeling conditions of DOTA-rituximab. Briefly, 10 mg of antibody previously purified by ultrafiltration device was conjugated with DOTA-NHS-ester (Macrocyclics) in 50 fold molar excess. The reaction was conducted for 1 hour in phosphate buffer pH 8.0 and gently mixing at room temperature, remaining for 24 hours under refrigeration. The immunoconjugated was purified by size exclusion column and ultrafiltration device. The radiolabeled parameters studied were: immunoconjugated mass, activity of {sup 177}LuCl{sub 3}, reaction time, temperature and pH. The radiochemical purity of the preparations was determined using analysis by thin layer chromatography (TLC-SG plates). The best studied condition presented radiochemical purity above 95% and the integrity of antibody was preserved. (author)

  19. Theoretical investigation on the geometries of DOTA and DOTA-like complexes and on the transition states of their conformational equilibria

    International Nuclear Information System (INIS)

    Computations, mostly at the RHF level, have been performed on La3+ and Y3+ model complexes of the widely used DOTA ligand [DOTA 1,4,7,10-tetra-aza-1,4,7,10-tetrakis(carboxy-methyl)cyclo-dodecane] for the purpose of identifying properties of the transition states of geometrical isomer inter-conversions, which have been the object of numerous NMR studies. An analogous study has been carried out on model complexes of the same tri-cations formed by the DOTA-like ligand 1,7-bis(1-methyl-imidazole-2-ylmethyl)-4,10-bis(carboxy-methyl)-1 4,7,10-tetra-aza-cyclo-dodecane, LH2. Features of the transition states for the two types of systems are compared. (authors)

  20. Photosensitization of Nanocrystalline TiO2 Electrode Modifiedwith C60 Carboxylic Acid Derivatives

    Institute of Scientific and Technical Information of China (English)

    张文; 史亚茹; 甘良兵; 黄春辉; 王艳琴; 虎民

    2001-01-01

    C60 carboxylic acid derivatives can be readily adsorbed on the surface of nanocrystalline TiO2 films act as charge-transfer sensitizer. The electron transport from TiO2 to the C60 derivatives results in the generation of the cathodic photocurrent. The short-circuit photocurrent of a C60 tetracarboxylic acid is 0.45 μA/cm2 under 464 um light illumination. The photoelectric behaviour of ITO electrodes modified by the same C60 carboxylic acids is different from that of the modified TiO2 electrodes, and shows anodic photocurrent.

  1. of radioconjugated DOTA-1-Nal3-octreotide labeled with gallium-68 using non-aqueous solvents

    International Nuclear Information System (INIS)

    Neuroendocrine tumors specifically over-expressing somatostatin receptors. Diagnosis has expanded due to radiolabelling of DOTA-peptides such as somatostatin analogue DOTA-1-Nal3-Octreotide (DOTA-NOC) conjugated to β+ emitting radionuclides such as 68Ga, which has very favorable physics-nuclear properties. This paper describes the radiolabeling procedures of DOTA-NOC with 68Ga, in pure aqueous medium and in presence of non-aqueous solvents as well as the methods used for quality control where a formulation is obtained with a radiochemical yield exceeding 95%. The addition of ethanol (30% - v / v) to reaction mixture allowed to increase the specific activity of 68Ga-DOTA-NOC radioconjugate, reaching a value of 182 MBq / nmol, higher than reported in the literature (50 MBq / nmol ) for labeling in pure aqueous medium. Stability studies are also presented (in presence of saline solution and saline phosphate buffer, transmetallation studies in Fe3+, Ca2+, Mg2+ and Zn2+ solutions, challenges competition against EDTA and DTPA chelators and in vitro stability in human transferrin) performed to 68Ga-DOTA-NOC radioconjugated, showing its high stability (> 95%). (author)

  2. Synthesis of tyrosine derivatives containing boric acid moiety

    Energy Technology Data Exchange (ETDEWEB)

    Kitazawa, M.; Yoshino, Kazuo [Shinshu Univ., Faculty of Science, Matsumoto, Nagano (Japan); Kimura, M.

    1998-12-01

    While p-boronophenylalanine (p-BPA) is known as a useful pharmaceutical for Boron Neutron Capture Therapy (BNCT), it is also reported that the boron content after it is accumulated in melanomas decreases gradually with time. 2-hydroxy-5-(2' carboxy-2'-aminoethyl) phenyl boric acid (HBPA) is suggested for alternative candidate to be used, as the compound (HBPA) resembles more in chemical nature to tyrosine and is more difficult to be oxidized by tyrosinase than p-BPA. The authors tried to synthesize HBPA via isocyanoethylacetate, employing 1-bromo-2-methoxy-5-methylbenzene as a starting material. The structure of the synthesized compounds at each steps in the course of the scheme was determined using {sup 1}H, {sup 13}C and {sup 11}B NMR spectrometer. (S. Ohno)

  3. Percutaneous absorption of nicotinic acid derivatives in vitro.

    Science.gov (United States)

    Dal Pozzo, A; Donzelli, G; Liggeri, E; Rodriguez, L

    1991-01-01

    The permeation rates through isolated epidermis of a homologous series of glycol, polyglycol, and alkyl esters of nicotinic acid were measured in vitro in a two-compartment diffusion cell assembly, using an isotonic buffered solution as the receiving phase. The esters were applied from aqueous solutions and also as the pure liquids. The results were consistent with those reported by other using compounds of equal or different structures either in vitro or in vivo. The experiments are compared in terms of partition equilibrium between vehicle and tissue and distribution from tissue to the receiving phase. It was demonstrated that the plateau observed in skin permeabilities of the compounds beyond a certain degree of lipophilicity is the result of the effect of water when used as the vehicle in the laboratory models. PMID:2013851

  4. Decay resistance of wood treated with boric acid and tall oil derivates.

    Science.gov (United States)

    Temiz, Ali; Alfredsen, Gry; Eikenes, Morten; Terziev, Nasko

    2008-05-01

    In this study, the effect of two boric acid concentrations (1% and 2%) and four derivates of tall oil with varying chemical composition were tested separately and in combination. The tall oil derivates were chosen in a way that they consist of different amounts of free fatty, resin acids and neutral compounds. Decay tests using two brown rot fungi (Postia placenta and Coniophora puteana) were performed on both unleached and leached test samples. Boric acid showed a low weight loss in test samples when exposed to fungal decay before leaching, but no effect after leaching. The tall oil derivates gave better efficacy against decay fungi compared to control, but are not within the range of the efficacy needed for a wood preservative. Double impregnation with boric acid and tall oil derivates gave synergistic effects for several of the double treatments both in unleached and leached samples. In the unleached samples the double treatment gave a better efficacy against decay fungi than tall oil alone. In leached samples a better efficacy against brown rot fungi were achieved than in samples with boron alone and a nearly similar or better efficacy than for tall oil alone. Boric acid at 2% concentration combined with the tall oil derivate consisting of 90% free resin acids (TO-III) showed the best performance against the two decay fungi with a weight loss less than 3% after a modified pure culture test.

  5. Synthesis, structure, and biological applications of α-fluorinated β-amino acids and derivatives.

    Science.gov (United States)

    March, Taryn L; Johnston, Martin R; Duggan, Peter J; Gardiner, James

    2012-11-01

    This review gives a broad overview of the state of play with respect to the synthesis, conformational properties, and biological activity of α-fluorinated β-amino acids and derivatives. General methods are described for the preparation of monosubstituted α-fluoro-β-amino acids (Scheme 1). Nucleophilic methods for the introduction of fluorine predominantly involve the reaction of DAST with alcohols derived from α-amino acids, whereas electrophilic sources of fluorine such as NFSI have been used in conjunction with Arndt-Eistert homologation, conjugate addition or organocatalyzed Mannich reactions. α,α-Difluoro-β-amino acids have also been prepared using DAST; however, this area of synthesis is largely dominated by the use of difluorinated Reformatsky reagents to introduce the difluoro ester functionality (Scheme 9). α-Fluoro-β-amino acids and derivatives analyzed by X-ray crystal and NMR solution techniques are found to adopt preferred conformations which are thought to result from stereoelectronic effects associated with F located close to amines, amides, and esters (Figs. 2-6). α-Fluoro amide and β-fluoro ethylamide/amine effects can influence the secondary structure of α-fluoro-β-amino acid-containing derivatives including peptides and peptidomimetics (Figs. 7-9). α-Fluoro-β-amino acids are also components of a diverse range of bioactive anticancer (e.g., 5-fluorouracil), antifungal, and antiinsomnia agents as well as protease inhibitors where such fluorinated analogs have shown increased potency and spectrum of activity.

  6. Metabolic Engineering of Yeast to Produce Fatty Acid-derived Biofuels: Bottlenecks and Solutions

    Directory of Open Access Journals (Sweden)

    Jiayuan eSheng

    2015-06-01

    Full Text Available Fatty acid-derived biofuels can be a better solution than bioethanol to replace petroleum fuel, since they have similar energy content and combustion properties as current transportation fuels. The environmentally friendly microbial fermentation process has been used to synthesize advanced biofuels from renewable feedstock. Due to their robustness as well as the high tolerance to fermentation inhibitors and phage contamination, yeast strains such as Saccharomyces cerevisiae and Yarrowia lipolytica have attracted tremendous attention in recent studies regarding the production of fatty acid-derived biofuels, including fatty acids, fatty acid ethyl esters, fatty alcohols, and fatty alkanes. However, the native yeast strains cannot produce fatty acids and fatty acid-derived biofuels in large quantities. To this end, we have summarized recent publications in this review on metabolic engineering of yeast strains to improve the production of fatty acid-derived biofuels, identified the bottlenecks that limit the productivity of biofuels, and categorized the appropriate approaches to overcome these obstacles.

  7. Comparison of 131I-TYR3-octreotate and 131I-DOTA-TYR3-octreotate: The effect of DOTA on pharmacokinetics and stability

    International Nuclear Information System (INIS)

    The authors compared the biodistribution, and in vivo and in vitro stabilities of 131I-Tyr3-octreotate and 131I-DOTA-Tyr3-octreotate. The peptides were radioiodinated by the chloramine T method and high radiochemical yields were obtained (greater than 97%). Both labelled compounds showed high stability when incubated in human plasma at 37 deg C. The 131I-Tyr3-octreotate showed significant hepatic uptake and biliary excretion. The biodistribution of 131I-DOTA-Tyr3-octreotate, however, can be compared with the distribution of radiometal labelled octreotide analogues. (author)

  8. Ent-kauren-19-oic acid derivatives from the stem bark of Croton pseudopulchellus Pax

    OpenAIRE

    Langat, MK; Mulholland, DA; Crouch, NR; Tammela, P; Pohjala, L; Smith, PJ

    2012-01-01

    Two new ent-kauren-19-oic acid derivatives, ent-14S*-hydroxykaur-16-en-19-oic acid and ent-14S*,17-dihydroxykaur-15-en-19-oic acid together with eleven known compounds ent-kaur-16-en-19-oic acid, ent-kaur-16-en-19-al, ent-12β-hydroxykaur-16-en-19-oic acid, ent-12β-acetoxykaur-16-en-19-oic acid, 8R,13R-epoxylabd-14-ene, eudesm-4(15)-ene-1β,6α-diol, (-)-7-epivaleran-4-one, germacra-4(15), 5E,10(14)-trien-9β-ol, acetyl aleuritolic acid, β-amyrin, and stigmasterol were isolated from the stem bark...

  9. Microbial production of amino acids and derived chemicals: synthetic biology approaches to strain development.

    Science.gov (United States)

    Wendisch, Volker F

    2014-12-01

    Amino acids are produced at the multi-million-ton-scale with fermentative production of l-glutamate and l-lysine alone being estimated to amount to more than five million tons in the year 2013. Metabolic engineering constantly improves productivities of amino acid producing strains, mainly Corynebacterium glutamicum and Escherichia coli strains. Classical mutagenesis and screening have been accelerated by combination with intracellular metabolite sensing. Synthetic biology approaches have allowed access to new carbon sources to realize a flexible feedstock concept. Moreover, new pathways for amino acid production as well as fermentative production of non-native compounds derived from amino acids or their metabolic precursors were developed. These include dipeptides, α,ω-diamines, α,ω-diacids, keto acids, acetylated amino acids and ω-amino acids. PMID:24922334

  10. Synthesis and pharmacology of N-alkylated derivatives of the excitotoxin ibotenic acid

    DEFF Research Database (Denmark)

    Madsen, U; Dumpis, M A; Bräuner-Osborne, Hans;

    1998-01-01

    Three amino-alkylated derivatives of the naturally occurring excitatory amino acid (EAA) receptor agonist ibotenic acid (Ibo) have been synthesized and tested pharmacologically. N-Methyl-Ibo (1a) and N-ethyl-Ibo (1b) were shown to be agonists at NMDA receptors (EC50 = 140 and 320 microM, respecti......Three amino-alkylated derivatives of the naturally occurring excitatory amino acid (EAA) receptor agonist ibotenic acid (Ibo) have been synthesized and tested pharmacologically. N-Methyl-Ibo (1a) and N-ethyl-Ibo (1b) were shown to be agonists at NMDA receptors (EC50 = 140 and 320 micro......-c and the potent NMDA agonist 2-amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid (AMAA) in order to elucidate the observed structure-activity data....

  11. Effect of the structure of gallic acid and its derivatives on their interaction with plant ferritin.

    Science.gov (United States)

    Wang, Qunqun; Zhou, Kai; Ning, Yong; Zhao, Guanghua

    2016-12-15

    Gallic acid and its derivatives co-exist with protein components in foodstuffs, but there is few report on their interaction with proteins. On the other hand, plant ferritin represents not only a novel class of iron supplement, but also a new nanocarrier for encapsulation of bioactive nutrients. However, plant ferritin is easy to be degraded by pepsin in the stomach, thereby limiting its application. Herein, we investigated the interaction of gallic acid and its derivatives with recombinant soybean seed H-2 ferritin (rH-2). We found that these phenolic acids interacted with rH-2 in a structure-dependent manner; namely, gallic acid (GA), methyl gallate (MEGA) and propyl gallate (PG) having three HO groups can bind to rH-2, while their analogues with two HO groups cannot. Consequently, such binding largely inhibited ferritin degradation by pepsin. These findings advance our understanding of the relationship between the structure and function of phenolic acids. PMID:27451180

  12. Molecular markers derived from bombesin for tumor diagnosis by SPECT and PET; Marcadores moleculares derivados da bombesina para diagnostico de tumores por SPECT e PET

    Energy Technology Data Exchange (ETDEWEB)

    Pujatti, Priscilla Brunelli

    2012-07-01

    A high number of molecules have already been identified to have high affinity to some receptors overexpressed on tumour cells and the radiolabelling of those molecules offers the possibility of new compounds for tumour diagnosis and therapy by nuclear medicine. Among of those molecules, bombesin (BBN) has become focus of interest, as its BB{sub 2} receptors are known to be overexpressed in prostate, breast, colon, pancreatic and lung tumour, as long as glioblastomas and neuroblastomas. BBN agonists and antagonists have already been described for this purpose and promising results were obtained in preclinical studies. However, most of them exhibited high abdominal accumulation, especially in pancreas and intestines, which can compromise diagnosis accuracy and cause serious adverse effects in therapy. In this context, the goal of the present work to radiolabel new BBN derivatives with {sup 11}1In and {sup 68}Ga and to evaluate their potential for BB{sub 2} positive tumors diagnosis by single photon emission tomography (SPECT) and positron emission tomography (PET). The structure of studied peptides was Q-YG{sub n}-BBN(6-14), where Q is the chelator, n is the number of glycine aminoacids in the spacer YG{sub n} and BBN(6-14) is the original bombesin sequence from the aminoacid 6 to 14. The derivative in which the last aminoacid (methionine, Met) was replaced by norleucine (Nle) was also evaluated. The experimental evaluation of the bombesin derivatives was divided into four steps: computational studies, molecular markers for SPECT, molecular markers for PET and toxicological studies. The theoretical partition (log P) and distribution (log D) coefficients were calculated for all bombesin derivatives conjugated to DTPA (diethylenetriaminepentaacetic acid) and DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) chelators applying computational programmes. Bombesin derivatives for SPECT were developed by radiolabelling DTPA-conjugated bombesin derivatives with

  13. Irbic acid, a dicaffeoylquinic acid derivative from Centella asiatica cell cultures.

    Science.gov (United States)

    Antognoni, Fabiana; Perellino, Nicoletta Crespi; Crippa, Sergio; Dal Toso, Roberto; Danieli, Bruno; Minghetti, Anacleto; Poli, Ferruccio; Pressi, Giovanna

    2011-10-01

    3,5-O-dicaffeoyl-4-O-malonilquinic acid (1) (irbic acid) has been isolated for the first time from cell cultures of Centella asiatica and till now it has never been reported to be present in the intact plant. Evidence of its structure was obtained by spectroscopic analyses (MS/NMR). Besides 1, cell cultures produce also the known 3,5-O-dicaffeoylquinic acid, chlorogenic acid, and the triferulic acid 2 (4-O-8'/4'-O-8″-didehydrotriferulic acid). Biological activities were evaluated for compound 1, which showed to have a strong radical scavenging capacity, together with a high inhibitory activity on collagenase. This suggests a possible utilization of this substance as a topical agent to reduce the skin ageing process. PMID:21635941

  14. Spectrophotometric study into complexing of vanadium(3) with salicylic acid derivatives

    International Nuclear Information System (INIS)

    Complexing of vanadium (3) with 5 amino-salicylic acid and amide of salicylhydroxamic acid has been studied. It has been shown that in acidic medium V3+ forms yellow complexes of the composition 1:1 with instability constants 2.2x10-19, 7.8x10-11, and 2.2x10-12, respectively. Complexes of V3+ with derivatives of salicylic acid can be used for determining V(3) content in the presence of V(4)

  15. Dosimetry of 64Cu-DOTA-AE105, a PET tracer for uPAR imaging

    International Nuclear Information System (INIS)

    64Cu-DOTA-AE105 is a novel positron emission tomography (PET) tracer specific to the human urokinase-type plasminogen activator receptor (uPAR). In preparation of using this tracer in humans, as a new promising method to distinguish between indolent and aggressive cancers, we have performed PET studies in mice to evaluate the in vivo biodistribution and estimate human dosimetry of 64Cu-DOTA-AE105. Methods: Five mice received iv tail injection of 64Cu-DOTA-AE105 and were PET/CT scanned 1, 4.5 and 22 h post injection. Volume-of-interest (VOI) were manually drawn on the following organs: heart, lung, liver, kidney, spleen, intestine, muscle, bone and bladder. The activity concentrations in the mentioned organs [%ID/g] were used for the dosimetry calculation. The %ID/g of each organ at 1, 4.5 and 22 h was scaled to human value based on a difference between organ and body weights. The scaled values were then exported to OLINDA software for computation of the human absorbed doses. The residence times as well as effective dose equivalent for male and female could be obtained for each organ. To validate this approach, of human projection using mouse data, five mice received iv tail injection of another 64Cu-DOTA peptide-based tracer, 64Cu-DOTA-TATE, and underwent same procedure as just described. The human dosimetry estimates were then compared with observed human dosimetry estimate recently found in a first-in-man study using 64Cu-DOTA-TATE. Results: Human estimates of 64Cu-DOTA-AE105 revealed the heart wall to receive the highest dose (0.0918 mSv/MBq) followed by the liver (0.0815 mSv/MBq), All other organs/tissue were estimated to receive doses in the range of 0.02–0.04 mSv/MBq. The mean effective whole-body dose of 64Cu-DOTA-AE105 was estimated to be 0.0317 mSv/MBq. Relatively good correlation between human predicted and observed dosimetry estimates for 64Cu-DOTA-TATE was found. Importantly, the effective whole body dose was predicted with very high precision

  16. Docosapentaenoic acid derived metabolites and mediators - The new world of lipid mediator medicine in a nutshell.

    Science.gov (United States)

    Weylandt, Karsten-H

    2016-08-15

    Recent years have seen the description and elucidation of a new class of anti-inflammatory and pro-resolving lipid mediators. The arachidonic acid (AA)-derived compounds in this class are called lipoxins and have been described in great detail since their discovery thirty years ago. The new players are mediators derived from fish oil omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), called resolvins, protectins and maresins. Taken together, these mediators are also called specialized pro-resolution mediators (SPMs). As compared to the AA/EPA/DHA-derived compounds, research regarding mediators formed from the n-3 and n-6 docosapentaenoic acids (DPAn-3 and DPAn-6) is sparse. However, mono- di- and trihydroxy derivates of the DPAs have anti-inflammatory properties as well, even though mechanisms of their anti-inflammatory action have not been fully elucidated. This review aims to summarize current knowledge regarding the DPA-derived SPMs and their actions. PMID:26546723

  17. Structure–anticancer activity relationships among 4-azolidinone-3-carboxylic acids derivatives

    Directory of Open Access Journals (Sweden)

    Lesyk R. B.

    2010-04-01

    Full Text Available The aim of present research was investigation of anticancer activity of 4-azolidinone-3-carboxylic acids derivatives, and studies of structure–activity relationships (SAR aspects. Methods. Organic synthesis; spectral methods; anticancer screening was performed according to the US NCI protocol (Developmental Therapeutic Program. Results. The data of new 4-thiazolidinone-3-alkanecarboxylic acids derivatives in vitro anticancer activity were described. The most active compounds which belong to 5-arylidene-2,4- thia(imidazolidinone-3-alkanecarboxylic acids; 5-aryl(heterylidenerhodanine-3-succinic acids derivatives were selected. Determination of some SAR aspects which allowed to determine directions in lead- compounds structure optimization, as well as desirable molecular fragments for design of potential anticancer agents based on 4-azolidinone scaffold were performed. 5-Arylidenehydantoin-3-acetic acids amides were identified as a new class of significant selective antileukemic agents. Possible pharmacophore scaffold of 5-ylidenerhodanine-3-succinic acids derivatives was suggested. Conclusions. The series of active compounds with high anticancer activity and/or selectivity levels were selected. Some SAR aspects were determined and structure design directions were proposed.

  18. Theophylline-7-acetic acid derivatives with amino acids as anti-tuberculosis agents.

    Science.gov (United States)

    Voynikov, Yulian; Valcheva, Violeta; Momekov, Georgi; Peikov, Plamen; Stavrakov, Georgi

    2014-07-15

    A series of amides were synthesized by condensation of theophylline-7-acetic acid and eight commercially available amino acid methyl ester hydrochlorides. Consecutive hydrolysis of six of the amido-esters resulted in the formation of corresponding amido-acids. The newly synthesized compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv. The activity varied depending on the amino acid fragments and in seven cases exerted excellent values with MICs 0.46-0.26 μM. Assessment of the cytotoxicity revealed that the compounds were not cytotoxic against the human embryonal kidney cell line HEK-293T. The theophylline-7-acetamides containing amino acid moieties appear to be promising lead compounds for the development of antimycobacterial agents.

  19. Synthesis of derivatives of tetronic acid and pulvinic acid. Total synthesis of norbadione A

    International Nuclear Information System (INIS)

    When vegetables like mushrooms are contaminated by radioactive caesium 137, this radioactive caesium is associated to norbadione A, a natural pigment present in two mushroom species and which can be used as a caesium decorporation agent or maybe as protection agent against ionizing radiations. Within this perspective, this research report describes the biosynthesis and the structure and properties of the norbadione A and of pulvinic acids (physicochemical properties, anti-oxidizing properties). Then, it presents the various tetronic acids (3-acyl-, 3-alkyl-, 3-alkoxy-, 3-aryl-tetronic acids and non 3-substituted tetronic acids), their synthesis path as they are described in the literature, and presents a new synthesis approach using a tandem reaction (with different esters or hydroxy esters) and the synthesis of tetronic acids. The author also proposes a new synthesis way for methyl pulvinates, and finally reports the work on the development of a total synthesis of the norbadione A

  20. The Effects of Malonic Acid Derivatives and Acetic Acid Derivatives as Coadsorbents on the Photovoltaic Performance of Dye-Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    Hiroaki Matsuyoshi

    2013-01-01

    Full Text Available The effects of malonic acid derivatives and acetic acid derivatives as coadsorbents on the photovoltaic performance of D908 dye-sensitized nanocrystalline TiO2 solar cells were investigated. Each of phenylmalonic acid (PMA and cyclopentylacetic acid (CPEAA coadsorptions was revealed to improve both the photocurrent and the photovoltage of the solar cells. The improved photocurrent was probably due to the suppression of self-quenching of the excited electrons in the dyes by coadsorption of PMA or CPEAA on the TiO2 that increased in the electron-injection yields from the dye to the TiO2. The improved photovoltage was probably due to suppression of recombination between the injected electrons and ions on the TiO2 surface. ATR-FTIR spectroscopy indicated that PMA or CPEAA coadsorption increased the content of bound dye on the TiO2 surface. This result suggests that PMA or CPEAA coadsorption improved the photocurrent of the solar cells. Electrochemical impedance spectroscopy indicated that PMA or CPEAA coadsorption on the TiO2 surface increased the charge recombination resistance (R2 and decreased the diffusion resistance in the electrolyte (R3. These results suggest that the coadsorption of PMA or CPEAA on the TiO2 may improve its photovoltage and photocurrent.

  1. New Biocompatible Polyesters Derived from α-Amino Acids: Hydrolytic Degradation Behavior

    Directory of Open Access Journals (Sweden)

    Jeoshua Katzhendler

    2010-10-01

    Full Text Available New polymers were synthesized from α-hydroxy acids derived from the natural amino acids Ile, Leu, Phe, and Val, combined with lactic acid, glycolic acid and 6-hydroxyhexanoic acid by direct condensation. The toxicity was determined and the degradation process of these polyesters was investigated under physiological conditions by analyzing the composition of the degraded polymers and the oligomers cleaved in the buffer medium. The polymers were found to be non toxic to two cell lines. Polymers displayed a biphasic degradation behavior. In most cases, a linear relationship was found between the weight loss constant and the hydrophobicity of the polymers, Log P. Regarding the second stage of weight loss, it is apparent that polymers derived from α-hydroxy(Lisoleucine ((LHOIle and α-hydroxy(LValine ((LHOVal degraded much faster than those derived from α-hydroxy(Lleucine ((LHOLeu and α-hydroxy(Lphenylalanine ((LHOPhe, probably due to different spatial orientation of the side chains. Copolymers of 6-hydroxyhexanoic acid displayed slow degradation rates as expected, whereas the degradation profile of copolymers of lactic acid was similar to the other homopolymers. These new polyesters may serve as potential biocompatible materials for medical applications.

  2. Ionic derivatives of betulinic acid as novel HIV-1 protease inhibitors.

    Science.gov (United States)

    Zhao, Hua; Holmes, Shaletha S; Baker, Gary A; Challa, Suresh; Bose, Himangshu S; Song, Zhiyan

    2012-10-01

    Betulinic acid is a natural product possessing abundant and favourable biological activity, including anti-cancer, anti-malarial, anti-inflammatory and anti-HIV properties, while causing minimal toxicity to unaffected cells. The full biological potency of betulinic acid cannot be fully unlocked, however, for a number of reasons, a primary one being its limited solubility in aqueous and biologically pertinent organic media. Aiming to improve the water solubility of betulinic acid without disrupting its structurally related bioactivity, we have prepared different ionic derivatives of betulinic acid. Inhibition bioassays on HIV-1 protease-catalysed peptide hydrolysis indicate significantly improved performance resulting from converting the betulinic acid to organic salt form. Indeed, for one particular cholinium-based derivative, its water solubility is improved more than 100 times and the half maximal inhibitory concentration (IC(50)) value (22 μg mL(-1)) was one-third that of wide-type betulinic acid (60 μg mL(-1)). These encouraging results advise that additional studies of ionic betulinic acid derivatives as a therapeutic solution against HIV-1 infection are warranted.

  3. Lanthanum(III) and praseodymium(III) derivatives with dithiocarbamates derived from α-amino acids

    Science.gov (United States)

    Rai, Anita; Sengupta, Soumitra K.; Pandey, Om P.

    2006-06-01

    Lanthanum(III) and praseodymium(III) complexes with dithiocarbamates have been synthesized by the reactions of lanthanum(III) and praseodymium(III) chloride with barium dithiocarbamate and complexes of type [LnCl(L)H 2O] n have been obtained (where Ln = La(III) or Pr(III); L = barium salt of dithiocarbamate derived from glycine, L-leucine, L-valine, DL-alanine). The complexes have been characterized by elemental analysis, molar conductance, electronic absorption and fluorescence, infrared, far infrared, 1H NMR spectral studies. The presence of coordinated water molecule is inferred from thermogravimetric analysis which indicates the loss of one water molecule at 150-170 °C. The oscillator strength, Judd-Ofelt intensity parameter, stimulated emission cross-section, etc. have been obtained for different transitions of Pr 3+.

  4. Ga(III) chelates of amphiphilic DOTA-based ligands: synthetic route and in vitro and in vivo studies

    Energy Technology Data Exchange (ETDEWEB)

    Fontes, Andre [Centro de Quimica, Campus de Gualtar, Universidade do Minho, 4710-057, Braga (Portugal); Prata, M. Isabel M. [IBILI, Faculdade de Medicina, Universidade de Coimbra, 3548, Coimbra (Portugal); Geraldes, Carlos F.G.C. [Departamento de Ciencias da Vida, Faculdade de Ciencias e Tecnologia, Universidade de Coimbra, 3001-401, Coimbra (Portugal); Centro de Neurociencias e Biologia Celular, Universidade de Coimbra, 3001-401, Coimbra (Portugal); Andre, Joao P., E-mail: jandre@quimica.uminho.p [Centro de Quimica, Campus de Gualtar, Universidade do Minho, 4710-057, Braga (Portugal)

    2011-04-15

    In this work, we report on a synthetic strategy using amphiphilic DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-based chelators bearing a variable-sized {alpha}-alkyl chain at one of the pendant acetate arms (from 6 to 14 carbon atoms), compatible with their covalent coupling to amine-bearing biomolecules. The amphiphilic behavior of the micelles-forming Ga(III) chelates (critical micellar concentration), their stability in blood serum and their lipophilicity (logP) were investigated. Biodistribution studies with the {sup 67}Ga-labeled chelates were performed in Wistar rats, which showed a predominant liver uptake with almost no traces of the radiochelates in the body after 24 h.

  5. Gadolinium(III-DOTA Complex Functionalized with BODIPY as a Potential Bimodal Contrast Agent for MRI and Optical Imaging

    Directory of Open Access Journals (Sweden)

    Matthias Ceulemans

    2015-11-01

    Full Text Available The synthesis and characterization of a novel gadolinium(III DOTA complex functionalized with a boron-dipyrromethene derivative (BODIPY is described. The assembly of the complex relies on azide diazotransfer chemistry in a copper tube flow reactor. The azide thus formed is coupled directly with an alkyne via click chemistry, resulting into a paramagnetic and luminescent gadolinium(III complex. Luminescent data and relaxometric properties of the complex have been evaluated, suggesting the potential applicability of the complexes as a bimodal contrast agent for magnetic resonance and optical imaging. The complex displays a bright emission at 523 nm with an absorption maximum of 507 nm and high quantum yields of up to 83% in water. The proton relaxivity of the complex measured at 310 K and at frequencies of 20 and 60 MHz had the values of 3.9 and 3.6 s−1·mM−1, respectively.

  6. Crystal Structure and Properties of the Carboxylic Acid Derivatives of Schizonpeta mulifida (L.) Briq.

    Institute of Scientific and Technical Information of China (English)

    LIU,Ju-Tao; YU,Ji-Cheng; JIANG,Hui-Ming; ZHANG,Li-Ying; ZHAO,Xiao-Jing; FAN,Sheng-Di

    2008-01-01

    The chemical constituents of the carboxylic acid derivatives from the ear of Schizonepeta were investigated,1H and 13C NMR chemical shifts of the carboxylic acid derivatives were accurately assigned.Two carboxylic acid derivative constituents were separated by a silica gel column.The structures were elucidated by the physical and chemical properties,IR,1H NMR,13C NMR,MALDI-TDF-MS and X-ray single crystal diffractometry.They were identified as 3-imino-N-(a-imidoethylamino)butyrolactam and neononane tetracid,respectively.The antitumoral activity on liver tumor ceils SMMC-7721 was determined in vitro.The experimental results showed that the former was better than the latter,and with increasing the concentration of the former the inhibitory activity was increased.

  7. Antitrypanosomal Activity of Novel Benzaldehyde-Thiosemicarbazone Derivatives from Kaurenoic Acid

    Directory of Open Access Journals (Sweden)

    Cecília M. A. de Oliveira

    2011-01-01

    Full Text Available A series of new thiosemicarbazones derived from natural diterpene kaurenoic acid were synthesized and tested against the epimastigote forms of Trypanosoma cruzi to evaluate their antitrypanosomal potential. Seven of the synthesized thiosemicarbazones were more active than kaurenoic acid with IC50 values between 2-24.0 mM. The o-nitro-benzaldehyde-thiosemicarbazone derivative was the most active compound with IC50 of 2.0 mM. The results show that the structural modifications accomplished enhanced the antitrypanosomal activity of these compounds. Besides, the thiocyanate, thiosemicarbazide and the p- methyl, p-methoxy, p-dimethylamine, m-nitro and o-chlorobenzaldehyde-thiosemicarbazone derivatives displayed lower toxicity for LLMCK2 cells than kaurenoic acid, exhibing an IC50 of 59.5 mM.

  8. 68Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice

    International Nuclear Information System (INIS)

    Increased expression of αvβ3/αvβ5 integrin is involved in angiogenesis and the inflammatory process in atherosclerotic plaques. The novel 68Ga-DOTA-RGD peptide binds with high affinity to αvβ3/αvβ5 integrin. The aim of this study was to investigate the uptake of the 68Ga-DOTA-RGD peptide in atherosclerotic plaques. Uptake of intravenously administered 68Ga-DOTA-RGD peptide was studied ex vivo in excised tissue samples and aortic sections of LDLR-/-ApoB100/100 atherosclerotic mice. The uptake of the tracer in aortic cryosections was examined by using digital autoradiography. Subsequently, the autoradiographs were combined with histological and immunohistological analysis of the sections. DOTA-RGD peptide was successfully labelled with the generator-produced 68Ga. The tracer had reasonably good specific radioactivity (8.7 ± 1.1 GBq/μmol) and was quite stable in vivo. According to ex vivo biodistribution results, 68Ga-DOTA-RGD was cleared rapidly from the blood circulation and excreted through the kidneys to the urine with high radioactivity in the intestine, lungs, spleen and liver. Autoradiography results showed significantly higher uptake of 68Ga-DOTA-RGD peptide in the atherosclerotic plaques compared to healthy vessel wall (mean ratio ± SD 1.4 ± 0.1, p = 0.0004). We observed that 68Ga-DOTA-RGD is accumulated into the plaques of atherosclerotic mice. However, this data only shows the feasibility of the approach, while the clinical significance still remains to be proven. Further studies are warranted to assess the uptake of this tracer into human atherosclerotic plaques. (orig.)

  9. Difficult diagnosis and localization of focal nesidioblastosis: clinical implications of 68Gallium-DOTA-D-Phe1-Tyr3-octreotide PET scanning

    Science.gov (United States)

    Kim, Jae Ri; Shin, Yong Chan; Cho, Young Min; Kim, Hongbeom; Kwon, Wooil; Han, Young Min; Kim, Sun-Whe

    2016-01-01

    Focal nesidioblastosis is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. Because it is difficult to localize and detect with current imaging modalities, nesidioblastosis is challenging for biliary-pancreatic surgeons. 68Gallium-DOTA-D-Phe1-Tyr3-octreotide PET scanning and 111indium-pentetreotide diethylene triamine pentaacetic acid octreotide scanning may be superior to conventional imaging modalities in determining the localization of nesidioblastosis. We report the successful surgical treatment of a 54-year-old woman with focal hyperplasia of the islets of Langerhans, who experienced frequent hypoglycemic symptoms and underwent various diagnostic examinations with different results. PMID:27433465

  10. Difficult diagnosis and localization of focal nesidioblastosis: clinical implications of (68)Gallium-DOTA-D-Phe(1)-Tyr(3)-octreotide PET scanning.

    Science.gov (United States)

    Kim, Jae Ri; Jang, Jin-Young; Shin, Yong Chan; Cho, Young Min; Kim, Hongbeom; Kwon, Wooil; Han, Young Min; Kim, Sun-Whe

    2016-07-01

    Focal nesidioblastosis is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. Because it is difficult to localize and detect with current imaging modalities, nesidioblastosis is challenging for biliary-pancreatic surgeons. (68)Gallium-DOTA-D-Phe(1)-Tyr(3)-octreotide PET scanning and (111)indium-pentetreotide diethylene triamine pentaacetic acid octreotide scanning may be superior to conventional imaging modalities in determining the localization of nesidioblastosis. We report the successful surgical treatment of a 54-year-old woman with focal hyperplasia of the islets of Langerhans, who experienced frequent hypoglycemic symptoms and underwent various diagnostic examinations with different results. PMID:27433465

  11. A Molecular Necklace: Threading β-Cyclodextrins onto Polymers Derived from Bile Acids.

    Science.gov (United States)

    Jia, Yong-Guang; Malveau, Cedric; Mezour, Mohamed A; Perepichka, Dmitrii F; Zhu, X X

    2016-09-19

    A molecular necklace of polypseudorotaxanes was prepared by threading β-cyclodextrins (β-CD) onto biodegradable and thermoresponsive polyurethanes derived from bile acids. These polyurethanes were synthesized via a simple step condensation of bile acid-based dicarbonate with poly(ethylene glycol)-diamine. The β-CD rings slide onto the poly(ethylene glycol) segments and selectively recognize the bile acid units of the polyurethane chains, whereas the poly(ethylene glycol) segments remain crystalline with a lower crystallinity. This bio-compound-derived molecular necklace can be visualized by scanning tunneling microscopy. The polypseudorotaxanes show thermosensitivity in water and the phase transition temperature may be fine-tuned by varying the molar ratios of β-CD to the bile acid units. Such an interesting necklace model of polypseudorotaxane constructed from natural compounds may lead to the further exploration of their applications, such as as an enzyme model, due to their biological nature. PMID:27558980

  12. Chlorophyll-derived fatty acids regulate expression of lipid metabolizing enzymes in liver - a nutritional opportunity

    Directory of Open Access Journals (Sweden)

    Wolfrum Christian

    2001-01-01

    Full Text Available Nutritional values of fatty acid classes are normally discussed on the basis of their saturated, monounsaturated and polyunsaturated structures with implicit understanding that they are straight-chain. Here we focus on chlorophyll-derived phytanic and pristanic acids that are minor isoprenoid branched-chain lipid constituents in food, but of unknown nutritional value. After describing the enzyme machinery that degrades these nutrient fatty acids in the peroxisome, we show by the criteria of a mouse model and of a human cell culture model that they induce with high potency expression of enzymes responsible for beta-oxidation of straight-chain fatty acids in the peroxisome. We summarize present mechanistic knowledge on fatty acid signaling to the nucleus, which involves protein/protein contacts between peroxisome proliferator activated receptor (PPAR and fatty acid binding protein (FABP. In this signaling event the branched-chain fatty acids are the most effective ones. Finally, on the basis of this nutrient-gene interaction we discuss nutritional opportunities and therapeutic aspects of the chlorophyll-derived fatty acids.

  13. Technological and economic potential of poly(lactic acid) and lactic acid derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Datta, R.; Tsai, S.P.; Bonsignore, P.; Moon, S.H.; Frank, J.R.

    1993-10-01

    Lactic acid has been an intermediate-volume specialty chemical (world production {approximately}40,000 tons/yr) used in a wide range of food processing and industrial applications. lactic acid h,as the potential of becoming a very large volume, commodity-chemical intermediate produced from renewable carbohydrates for use as feedstocks for biodegradable polymers, oxygenated chemicals, plant growth regulators, environmentally friendly ``green`` solvents, and specially chemical intermediates. In the past, efficient and economical technologies for the recovery and purification of lactic acid from crude fermentation broths and the conversion of tactic acid to the chemical or polymer intermediates had been the key technology impediments and main process cost centers. The development and deployment of novel separations technologies, such as electrodialysis (ED) with bipolar membranes, extractive distillations integrated with fermentation, and chemical conversion, can enable low-cost production with continuous processes in large-scale operations. The use of bipolar ED can virtually eliminate the salt or gypsum waste produced in the current lactic acid processes. In this paper, the recent technical advances in tactic and polylactic acid processes are discussed. The economic potential and manufacturing cost estimates of several products and process options are presented. The technical accomplishments at Argonne National Laboratory (ANL) and the future directions of this program at ANL are discussed.

  14. Novel self-associative and multiphase nanostructured soft carriers based on amphiphilic hyaluronic acid derivatives

    DEFF Research Database (Denmark)

    Eenschooten, Corinne; Vaccaro, Andrea; Delie, Florence;

    2012-01-01

    The purpose of the present study was to investigate the physicochemical properties in aqueous media of amphiphilic hyaluronic acid (HA) derivatives obtained by reaction of HA’s hydroxyl groups with octenyl succinic anhydride (OSA). The self-associative properties of the resulting octenyl succinic...... anhydridemodified hyaluronic acid (OSA-HA) derivatives were studied by fluorescence spectroscopy using Nile Red as fluorophore. The morphology, size and surface charge of the OSA-HA assemblies were determined by transmission electron microscopy, dynamic light scattering and by measuring their electrophoretic...

  15. Promise of Retinoic Acid-Triazolyl Derivatives in Promoting Differentiation of Neuroblastoma Cells.

    Science.gov (United States)

    Lone, Ali Mohd; Dar, Nawab John; Hamid, Abid; Shah, Wajaht Amin; Ahmad, Muzamil; Bhat, Bilal A

    2016-01-20

    Retinoic acid induces differentiation in various types of cells including skeletal myoblasts and neuroblasts and maintains differentiation of epithelial cells. The present study demonstrates synthesis and screening of a library of retinoic acid-triazolyl derivatives for their differentiation potential on neuroblastoma cells. Click chemistry approach using copper(I)-catalyzed azide-alkyne cycloaddition was adopted for the preparation of these derivatives. The neurite outgrowth promoting potential of retinoic acid-triazolyl derivatives was studied on neuroblastoma cells. Morphological examination revealed that compounds 8a, 8e, 8f, and 8k, among the various derivatives screened, exhibited promising neurite-outgrowth inducing activity at a concentration of 10 μM compared to undifferentiated and retinoic acid treated cells. Further on, to confirm this differentiation potential of these compounds, neuroblastoma cells were probed for expression of neuronal markers such as NF-H and NeuN. The results revealed a marked increase in the NF-H and NeuN protein expression when treated with 8a, 8e, 8f, and 8k compared to undifferentiated and retinoic acid treated cells. Thus, these compounds could act as potential leads in inducing neuronal differentiation for future studies.

  16. Effect of vanillin and its acid and alcohol derivatives on the diphenolase activity of mushroom tyrosinase

    OpenAIRE

    Masoomeh Bagheri-Kalmarzi; Sajedi, Reza H.; Elham Asadollahi; Nosrat O. Mahmoodi; Reza Haji-Hosseini

    2012-01-01

    For the first time in the present study the effects of vanillin, vanillyl alcohol, vanillic acid, as well as the newly synthesized vanillin derivative, bis-vanillin, were investigated on the oxidation of dopamine hydrochloride by mushroom tyrosinase. Among them, vanillin and bis-vanillin act as activators, while vanillyl alcohol and vanillic acid exhibited inhibitory effects, the IC50 values being estimated 1.5 and 1.0 mM, respectively. These compounds were mixed inhibitors. The presence of a...

  17. Cytotoxicity of Coprinopsis atramentaria extract, organic acids and their synthesized methylated and glucuronate derivatives

    OpenAIRE

    Heleno, Sandrina A.; Isabel C. F. R. Ferreira; Calhelha, Ricardo C.; Esteves, Ana P.; Martins, Anabela; Queiroz, Maria João R. P.

    2014-01-01

    Coprinopsis atramentaria is a wild edible mushroom whose methanolic extract revealed a marked antioxidant activity; p-hydroxybenzoic (HA), p-coumaric (CoA) and cinnamic (CA) acids were identified in the extract. In the present work, the cytotoxicity of C. atramentaria extract, previously identified organic acids and their synthesized derivatives (methylated compounds and protected glucuronides) was evaluated. Among all the tested cell lines (MCF-7—breast adenocarcinoma, NCI-H460—non-small cel...

  18. Synthesis and Quantitative Structure-Property Relationships of Side Chain-Modified Hyodeoxycholic Acid Derivatives

    OpenAIRE

    Antimo Gioiello; Antonio Macchiarulo; Roberto Pellicciari; Roberto Nuti; Roccaldo Sardella; Benedetto Natalini; Paola Sabbatini; Paolo Filipponi

    2013-01-01

    Bile acids have emerged as versatile signalling compounds of a complex network of nuclear and membrane receptors regulating various endocrine and paracrine functions. The elucidation of the interconnection between the biological pathways under the bile acid control and manifestations of hepatic and metabolic diseases have extended the scope of this class of steroids for in vivo investigations. In this framework, the design and synthesis of novel biliary derivatives able to modulate a specific...

  19. Phenolic Acids, Phenolic Aldehydes and Furanic Derivatives in Oak Chips: American vs. French Oaks

    OpenAIRE

    Cabrita, M.J.; Barrocas Dias, C.; Costa Freitas, A.M.

    2011-01-01

    Phenolic acids (gallic, vanillic, syringic and ellagic acids), phenolic aldehydes (vanillin, syringaldehyde, coniferaldehyde and sinapaldehyde) and furanic derivatives (furfural, 5-methylfurfural and 5-hydroxymethylfurfural) were quantified in commercial American and French oak chips. Chips with different sizes and toast degrees were used. Compounds were extracted directly from the wood samples in order to determine possible differences among woods as well as toast degree. Likewise, the compo...

  20. The Effect of the Serum Amino Acid Levels Thiosemicarbazone Derivatives and its Metal Complexes on Rats

    OpenAIRE

    Karatepe, Mustafa; Kaman, Dilara

    2013-01-01

    Advers biological activities of Thiosemicarbazone (TSC) and Schiff base (SB) derivatives have been widely studied in rats and in other animal species using different doses, times and routes of administration. To date, no attempt has been made to study alterations occurring in the amino acid profile in the effects of the thiosemicarbazone derivative and its metal complexes on the rats. At this study, the rats were injected subcutaneously with a new thiosemicarbazone and its LH-Zn and LH-Cu com...

  1. Cyclic derivatives of D-glucose and tartaric acid as building blocks for renewable polyesters

    OpenAIRE

    Japu, Cristina

    2014-01-01

    Three series of aromatic copolyesters derived from poly(ethylene terephthalate) (PET), poly(butylene terephthalate) (PBT) and poly(hexamethylene terephthalate) (PHT) have been synthesized by melt polycondensation in which the terephthalate and oxyalkylene units have been partially or totally replaced by monocyclic and bicyclic diacids and diols obtained by derivatization of renewable monomers such as tartaric acid and D-glucose respectively. Another series of aliphatic copolyesters derived f...

  2. A Direct, Biomass-Based Synthesis of Benzoic Acid: Formic Acid-Mediated Deoxygenation of the Glucose-Derived Materials Quinic Acid and Shikimic Acid

    Energy Technology Data Exchange (ETDEWEB)

    Arceo, Elena; Ellman, Jonathan; Bergman, Robert

    2010-05-03

    An alternative biomass-based route to benzoic acid from the renewable starting materials quinic acid and shikimic acid is described. Benzoic acid is obtained selectively using a highly efficient, one-step formic acid-mediated deoxygenation method.

  3. Preparation and adsorption behavior for metal ions and humic acid of chitosan derivatives crosslinked by irradiation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This article deals with the determination of the adsorption properties of metal ions and humic acid in water on crosslinked chitosan derivatives (carboxymethylchitosan) which were formed using the irradiation technique without any additives. The solubility test of these crosslinked materials were investigated in acidic, alkaline media,distilled water, and certain organic solvents. Scanning electron microscopic (SEM) images showed that the crosslinked chitosan derivatives possessed a porous morphological structure. Charged characteristic analyses demonstrated typically pH-dependent properties of the crosslinked materials. The adsorption studies were carried out by the batch method at room temperature. Adsorption of heavy metal ions (such as Cu2+, Cd2+) and humic acid onto crosslinked samples was found to be strongly pH-dependent. Adsorption kinetic studies indicated the rapid removal of metal ions, and humic acid from the aqueous solutions. Moreover, isothermal adsorption data revealed that Cu2+, Cd2+,and humic acid were removed by these crosslinked materials with high efficiency. Adsorption isothermal data were interpreted well by the Langmuir equation. These crosslinked carboxymethylated chitosan derivatives indicate favorable adsorption of metal ions and humic acid.

  4. Implications for eicosapentaenoic acid- and docosahexaenoic acid-derived resolvins as therapeutics for arthritis.

    Science.gov (United States)

    Souza, Patricia R; Norling, Lucy V

    2016-08-15

    Omega-3 polyunsaturated fatty acids are essential for health and are known to possess anti-inflammatory properties, improving cardiovascular health as well as benefiting inflammatory diseases. Indeed, dietary supplementation with omega-3 polyunsaturated fatty acids has proved efficacious in reducing joint pain, morning stiffness and nonsteroidal anti-inflammatory drugs usage in rheumatoid arthritis patients. However, the mechanisms by which omega-3 polyunsaturated fatty acids exert their beneficial effects have not been fully explored. Seminal discoveries by Serhan and colleagues have unveiled a novel class of bioactive lipid mediators that are enzymatically biosynthesized in vivo from omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), termed resolvins, protectins and maresins. These bioactive pro-resolving lipid mediators provide further rationale for the beneficial effects of fish-oil enriched diets. These endogenous lipid mediators are spatiotemporally biosynthesized to actively regulate resolution by acting on specific G protein-coupled receptors (GPCRs) to initiate anti-inflammatory and pro-resolving signals that terminate inflammation. In this review, we will discuss the mechanism of actions of these molecules, including their analgesic and bone-sparing properties making them ideal therapeutic agonists for the treatment of inflammatory diseases such as rheumatoid arthritis. PMID:26165764

  5. Safety assessment of animal- and plant-derived amino acids as used in cosmetics.

    Science.gov (United States)

    Burnett, Christina; Heldreth, Bart; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

    2014-01-01

    The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of animal- and plant-derived amino acid mixtures, which function as skin and hair conditioning agents. The safety of α-amino acids as direct food additives has been well established, based on extensive research through acute and chronic dietary exposures and the Panel previously has reviewed the safety of individual α-amino acids in cosmetics. The Panel focused its review on dermal irritation and sensitization data relevant to the use of these ingredients in topical cosmetics. The Panel concluded that these 21 ingredients are safe in the present practices of use and concentration as used in cosmetics.

  6. 68Ga-DOTA0-Tyr3-octreotide positron emission tomography in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    PET/CT with 68Ga-labelled [DOTA0,Tyr3]-octreotide (68Ga-DOTA-TOC PET/CT) is a routinely used imaging modality for neuroendocrine tumours expressing somatostatin receptors (SSTR). Recent studies have shown SSTR expression in head and neck squamous cell carcinoma, albeit lower than in highly differentiated neuroendocrine tumours. We sought to determine whether nasopharyngeal carcinoma (NPC) positive for Epstein-Barr virus (EBV), a rare subtype of head and neck cancer, shows increased 68Ga-DOTA-TOC uptake indicating expression of SSTR. Five patients with untreated, histologically proven EBV-positive NPC were referred for 68Ga-DOTA-TOC PET/CT. Tracer uptake in tumour lesions was assessed visually and semiquantitatively measuring maximum standardized uptake values (SUVmax) and tumour to background ratios. Increased tumour-specific uptake was detected in all five patients with a median SUVmax of 10.6 (range 3.6 - 17.1) in the primary tumour and 13.2 (range 6.1 - 14.5) in cervical lymph node metastases. 68Ga-DOTA-TOC PET/CT demonstrated tracer uptake in EBV-positive NPC comparable to that in highly differentiated neuroendocrine tumours. This observation is consistent with increased SSTR expression in EBV-positive NPC and may open new diagnostic and therapeutic windows in NPC. (orig.)

  7. Gd-DOTA enhancement of cerebral and spinal tumors on MR imaging

    International Nuclear Information System (INIS)

    The use of Gd-DOTA as a contrast agent in MR imaging to improve the diagnosis of cerebral and spinal tumors was assessed in 20 patients, ten with brain tumors and ten with spinal tumors. Imaging was performed with a 0.5-T Magniscan 5000 unit. T1-weighted (spin-echo and gradient-echo) and T2-weighted (spin-echo) images were acquired before and after intravenous injection of Gd-DOTA, 0.1 mmol/kg. On T1-weighted images, Gd-DOTA enhanced sites of presumed disruption of the blood-brain barrier. This made some brain tumors more conspicuous and helped target biopsies, but did not reveal any additional lesions. On the other hand, the use of Gd-DOTA significantly improved the reliability of spinal tumor imaging compared to imaging performed without contrast agent, allowing delineation of abnormalities on T1-weighted images, which frequently contain fewer artifacts than the most sensitive T2-weighted images. Images obtained with Gd-DOTA could be used by the physician to rule out residual tumor after surgery and to assess recurrences. Additional work should be done to discover whether spinal tumor exploration with MR imaging could include solely T1-weighted sequences, performed before and after contrast agent administration, without T2-weighted sequences

  8. Synthesis and Quantitative Structure-Property Relationships of Side Chain-Modified Hyodeoxycholic Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Antimo Gioiello

    2013-08-01

    Full Text Available Bile acids have emerged as versatile signalling compounds of a complex network of nuclear and membrane receptors regulating various endocrine and paracrine functions. The elucidation of the interconnection between the biological pathways under the bile acid control and manifestations of hepatic and metabolic diseases have extended the scope of this class of steroids for in vivo investigations. In this framework, the design and synthesis of novel biliary derivatives able to modulate a specific receptor requires a deep understanding of both structure-activity and structure-property relationships of bile acids. In this paper, we report the preparation and the critical micellization concentration evaluation of a series of hyodeoxycholic acid derivatives characterized by a diverse side chain length and by the presence of a methyl group at the alpha position with respect to the terminal carboxylic acid moiety. The data collected are instrumental to extend on a quantitative basis, the knowledge of the current structure-property relationships of bile acids and will be fruitful, in combination with models of receptor activity, to design and prioritize the synthesis of novel pharmacokinetically suitable ligands useful in the validation of bile acid-responsive receptors as therapeutic targets.

  9. Bile acid derivatives as ligands of the farnesoid x receptor: molecular determinants for bile acid binding and receptor modulation.

    Science.gov (United States)

    Gioiello, Antimo; Cerra, Bruno; Mostarda, Serena; Guercini, Chiara; Pellicciari, Roberto; Macchiarulo, Antonio

    2014-01-01

    Bile acids are a peculiar class of steroidal compounds that never cease to amaze. From being simple detergents with a primary role in aiding the absorption of fats and fat-soluble vitamins, bile acids are now widely considered as crucial hormones endowed with genomic and non-genomic functions that are mediated by their interaction with several proteins including the nuclear receptor Farnesoid X Receptor (FXR). Taking advantages of the peculiar properties of bile acids in interacting with the FXR receptor, several biliary derivatives have been synthesized and tested as FXR ligands. The availability of these compounds has contributed to characterize the receptor from a structural, patho-physiological and therapeutic standpoint. Among these, obeticholic acid is a first-in-class FXR agonist that is demonstrating hepatoprotective effects upon FXR activation in patients with liver diseases such as primary biliary cirrhosis and nonalcoholic steatohepatitis. This review provides an historical overview of the rationale behind the discovery of obeticholic acid and chemical tools generated to depict the molecular features and bio-pharmacological relevance of the FXR receptor, as well as to summarize structure-activity relationships of bile acid-based FXR ligands so far reported. PMID:25388535

  10. Free and bound cinnamic acid derivatives in corsica sweet blond oranges.

    Science.gov (United States)

    Carrera, Eric; El Kebir, Mohamed Vall Ould; Jacquemond, Camille; Luro, François; Lozano, Yves; Gaydou, Emile M

    2010-03-01

    Total determination of cinnamic acids (CA), including hydroxycinnamic acid derivatives is generally not accurate since, during hydrolysis, a possible degradation of dihydroxy CA such as caffeic acid could occur. Evaluations of CA (ferulic, p-coumaric, sinapic, cinnamic and caffeic acids) before and after hydrolysis have been undertaken using standards and either with or without addition of ascorbic acid and EDTA. The method was then applied to the determination of free and bound CA in five blond cultivars (Navelina, Washington navel, Pera, Salustiana and Valencia late) of sweet oranges [Citrus sinensis (L.) Osb.]. Four parts of the fruits (peel juice, flavedo, albedo and juice) have been investigated. Results show that CA are mainly bound (86% up to 92%) in the four fruit parts. The mean of total CA contents was found to be higher in peel juice (1.5 g kg(-1)) in comparison with flavedo (0.7 g kg(-1)), albedo (0.1 g kg(-1)) and juice (0.6 g kg(-1)). Free and bound ferulic acid represented 55-70% of CA in juices, followed by p-coumaric acid (20%), sinapic acid (10%) and caffeic acid (9%). Total contents of each CA in the four fruit parts are discussed and show the potential interest in orange peel wastes. PMID:20420324

  11. Simultaneous determination of 2-naphthoxyacetic acid and indole-3-acetic acid by first derivation synchronous fluorescence spectroscopy

    Science.gov (United States)

    Liu, Xiangxiang; Wan, Yiqun

    2013-07-01

    A simple, rapid, sensitive and selective method for simultaneously determining 2-naphthoxyacetic acid (BNOA) and Indole-3-Acetic Acid (IAA) in mixtures has been developed using derivation synchronous fluorescence spectroscopy based on their synchronous fluorescence. The synchronous fluorescence spectra were obtained with Δλ = 100 nm in a pH 8.5 NaH2PO4-NaOH buffer solution, and the detected wavelengths of quantitative analysis were set at 239 nm for BNOA and 293 nm for IAA respectively. The over lapped fluorescence spectra were well separated by the synchronous derivative method. Under optimized conditions, the limits of detection (LOD) were 0.003 μg/mL for BNOA and 0.012 μg/mL for IAA. This method is simple and expeditious, and it has been successfully applied to the determination of 2-naphthoxyacetic acid and indole-3-acetic acid in fruit juice samples with satisfactory results. The samples were only filtrated through a 0.45 μm membrane filter, which was free from the tedious separation procedures. The obtaining recoveries were in the range of 83.88-87.43% for BNOA and 80.76-86.68% for IAA, and the relative standard deviations were all less than 5.0%. Statistical comparison of the results with high performance liquid chromatography Mass Spectrometry (HPLC-MS) method revealed good agreement and proved that there were no significant difference in the accuracy and precision between these two methods.

  12. Heterogeneous catalysts for the transformation of fatty acid triglycerides and their derivatives to fuel hydrocarbons

    International Nuclear Information System (INIS)

    The results of studies devoted to the catalysts for transformation of fatty acid triglycerides and their derivatives to fuel hydrocarbons are presented and described systematically. Various approaches to the use of heterogeneous catalysts for the production of biofuel from these raw materials are considered. The bibliography includes 134 references.

  13. Silica Sulfuric Acid: An Eco-Friendly and Reusable Catalyst for Synthesis of Benzimidazole Derivatives

    Directory of Open Access Journals (Sweden)

    Bahareh Sadeghi

    2013-01-01

    Full Text Available Silica sulfuric acid (SiO2-OSO3H as an eco-friendly, readily available, and reusable catalyst is applied to benzimidazole derivatives synthesis under reflux in ethanol. The procedure is very simple and the products are isolated with an easy workup in good-to-excellent yields.

  14. Synthesis and bioactivity of novel nitric oxide-releasing ursolic acid derivatives

    Institute of Scientific and Technical Information of China (English)

    Li Chen; Wen Qiu; Jia Tang; Zhi Feng Wang; Shu Ying He

    2011-01-01

    A series of furoxan-based novel nitric oxide-donating ursolic acid (UA) derivatives (7a-f) were synthesized, and their cytotoxic activities against HepG2 cells in vitro were evaluated by MTT method. It was found that 7a-d and 7f showed more potent cytotoxic activities than control 5-fluorouracil and UA.

  15. Multilayer Film Fabrication and Photoelectric Conversion Property of Two Pyrrolidinofullerene Carboxylic Acid Derivatives

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Two multilayer films of pyrrolidinofullerene carboxylic acid derivatives, which exhibit photoelectric conversion property, are reported here. The first monolayers were fabricated on hydrophilic indium-tin-oxide (ITO), quartz, and mica by esterification reaction. The multilayers were characterized by contact angle and UV spectrum. The photoelectric conversion properties of both multilayer films were studied.

  16. An Unexpected and Efficient Synthesis of Open-chain Derivatives of Bistetronic Acid under Microwave Irradiation

    Institute of Scientific and Technical Information of China (English)

    SHI Feng; MA Ning; ZHOU Dianxiang; ZHANG Ge; JIANG Bo; TU Shujiang

    2009-01-01

    An unexpected and efficient synthesis of novel open-chain derivatives of bistetronic acid has been successfully achieved in glyclol under microwave irradiation (MW).This method has the prominent advantages of short reaction time,high yield,operational simplicity as well as environmental friendliness.

  17. Nonmetal catalyzed insertion reactions of diazocarbonyls to acid derivatives in fluorinated alcohols.

    Science.gov (United States)

    Dumitrescu, Lidia; Azzouzi-Zriba, Kaouther; Bonnet-Delpon, Danièle; Crousse, Benoit

    2011-02-18

    The insertion reaction of diazocarbonyls to acids could be performed smoothly in fluorinated alcohols in the absence of metal catalyst. This new procedure allowed the chemoselective preparation of various functionalized compounds such as acyloxyesters, depsipeptides, and sulfonate, phosphonate, or boronate derivatives.

  18. Aggregation behavior of cholic acid derivatives in organic solvents and in water

    NARCIS (Netherlands)

    Willemen, H.M.

    2002-01-01

    In this thesis various cholic acid derivatives are reported that display aggregation in water or in organic solvents. Spontaneous aggregation of single molecules into larger, ordered structures occurs at the borderline of solubility. Amphiphilic compounds, or surfactants, which possess a hydrophobic

  19. Polyhydroxyalkanoate-based 3-hydroxyoctanoic acid and its derivatives as a platform of bioactive compounds.

    Science.gov (United States)

    Radivojevic, Jelena; Skaro, Sanja; Senerovic, Lidija; Vasiljevic, Branka; Guzik, Maciej; Kenny, Shane T; Maslak, Veselin; Nikodinovic-Runic, Jasmina; O'Connor, Kevin E

    2016-01-01

    A library of 18 different compounds was synthesized starting from (R)-3-hydroxyoctanoic acid which is derived from the bacterial polymer polyhydroxyalkanoate (PHA). Ten derivatives, including halo and unsaturated methyl and benzyl esters, were synthesized and characterized for the first time. Given that (R)-3-hydroxyalkanoic acids are known to have biological activity, the new compounds were evaluated for antimicrobial activity and in vitro antiproliferative effect with mammalian cell lines. The presence of the carboxylic group was essential for the antimicrobial activity, with minimal inhibitory concentrations against a panel of bacteria (Gram-positive and Gram-negative) and fungi (Candida albicans and Microsporum gypseum) in the range 2.8-7.0 mM and 0.1-6.3 mM, respectively. 3-Halogenated octanoic acids exhibited the ability to inhibit C. albicans hyphae formation. In addition, (R)-3-hydroxyoctanoic and (E)-oct-2-enoic acids inhibited quorum sensing-regulated pyocyanin production in the opportunistic pathogen Pseudomonas aeruginosa PAO1. Generally, derivatives did not inhibit mammalian cell proliferation even at 3-mM concentrations, while only (E)-oct-2-enoic and 3-oxooctanoic acid had IC50 values of 1.7 and 1.6 mM with the human lung fibroblast cell line. PMID:26399414

  20. Evaluation of preservative effectiveness of p-coumaric acid derivatives in aluminium hydroxide gel-USP

    Directory of Open Access Journals (Sweden)

    Anurag Khatkar

    2013-01-01

    Full Text Available Background: Deterioration of pharmaceutical preparations due to growth of microorganisms is a great challenge and need of preservation becomes very important. Literature reports about various problems associated with the existing synthetic preservatives such as development of microbial resistance (in due course of time and several serious side effects. Aim: The aim of the present study is to find out new preservatives synthesized from natural sources, which may have better efficiency than the existing synthetic preservatives. The derivatives of naturally occurring p-coumaric acid were subjected for their preservative efficacy study. Their preservative efficiency was evaluated and compared with the standard parabens. Materials and Methods: The selected amide, anilide and ester derivatives of p-coumaric acid were subjected to preservative efficacy testing in an official antacid preparation, (aluminium hydroxide gel-USP against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Candida albicans and Aspergillus niger as representative challenging microorganisms as per USP 2004 guidelines. Results: The selected derivatives were found to be effective against all selected strains and showed preservative efficacy comparable to that of standard and even better in case E. coli, C. albicans and A. niger. The 8-hydroxy quinoline ester derivative showed better preservative efficacy than standard as well as other derivatives. Conclusion: The newly synthesized p- coumaric acid preservatives were found to be effective in the proposed pharmaceutical preparation (Aluminium Hydroxide Gel - USP. Also, the synthesized preservatives have shown comparative and even better efficacy than the existing parabens and hence they have potential for use in pharmaceutical preparations.

  1. Evaluation of preservative effectiveness of gallic acid derivatives in aluminum hydroxide gel-USP

    Directory of Open Access Journals (Sweden)

    Anurag Khatkar

    2013-01-01

    Full Text Available Background: Preservatives are added to most of the pharmaceutical preparations to prevent them from deterioration throughout their shelf life. Literature reveals that the common synthetic preservatives have many limitations, such as development of microbial resistance (in due course of time and several serious side-effects. Aim: The aim of this study is to find out new preservatives synthesized from natural sources, which may have better efficiency than the existing synthetic preservatives. The derivatives of naturally occurring gallic acid were subjected for their preservative efficacy study. Their preservative efficiency was evaluated and compared with the standard parabens. Materials and Methods: The selected amide, anilide and ester derivatives of gallic acid were subjected to preservative efficacy testing in an official antacid preparation, {aluminum hydroxide gel-USP (United States Pharmacopoeia} against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Candida albicans, and Aspergillus niger as representative challenging microorganisms as per USP 2004 guidelines. Results: The selected derivatives were found to be effective against all selected strains and showed preservative efficacy comparable to that of standard and even better in case E. coli, C. albicans and A. niger. The 8-hydroxy quinoline ester derivative showed better preservative efficacy than standard as well as other derivatives. Conclusion: The newly synthesized gallic acid preservatives were found to be effective in the proposed pharmaceutical preparation (Aluminium Hydroxide Gel - USP. Also, the synthesized preservatives have shown comparative and even better efficacy than the existing parabens and hence they have potential for use in pharmaceutical preparations.

  2. Dosimetry of 64Cu-DOTA-AE105, a PET tracer for uPAR imaging

    DEFF Research Database (Denmark)

    Persson, Morten; El Ali, Henrik H.; Binderup, Tina;

    2014-01-01

    of another 64Cu-DOTA peptide-based tracer, 64Cu-DOTA-TATE, and underwent same procedure as just described. The human dosimetry estimates were then compared with observed human dosimetry estimate recently found in a first-in-man study using 64Cu-DOTA-TATE. ResultsHuman estimates of 64Cu-DOTA-AE105 revealed...... between human predicted and observed dosimetry estimates for 64Cu-DOTA-TATE was found. Importantly, the effective whole body dose was predicted with very high precision (predicted value: 0.0252mSv/Mbq, Observed value: 0.0315mSv/MBq) thus validating our approach for human dosimetry estimation. Conclusion...

  3. Influence of organic acids on UV-Vis spectra of pyrrolidino- [60]fullerene derivatives

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A pyrrolidino[60]fullerene 1 with pyrrolidine group was synthesized and characterized. The UV-Vis spectra showed that the blue shift of absorption peaks was first observed when strong organic acids such as p-toluene sulfonic or trifluoroacetic acid were added to the solution of pyrrolidino[60]fullerene 1 in dichloromethane. The results indicated that the pyrrolidino[60]fullerene derivatives without pyrrolidine group also possess the same phenomenon. Experiments and computation with the MOPAC 7.0 semi-em- pirical PM3 method demonstrated the reason that some energy gaps on [60]fullerene skeleton were increased because electronic charges on [60]fullerene framework transferred to pyrrolidine ring when strong organic acids were added into pyrrolidino[60]fullerene derivatives' solution; as the result, the complexes could be formed and some absorption wave-lengths blue shifted in the UV-Vis spectrum.

  4. In situ forming hydrogels of hyaluronic acid and inulin derivatives for cartilage regeneration.

    Science.gov (United States)

    Palumbo, Fabio S; Fiorica, Calogero; Di Stefano, Mauro; Pitarresi, Giovanna; Gulino, Alessandro; Agnello, Stefano; Giammona, Gaetano

    2015-05-20

    An in situ forming hydrogel obtained by crosslinking of amino functionalized hyaluronic acid derivatives with divinylsulfone functionalized inulin (INU-DV) has been here designed and characterized. In particular two hyaluronic acid derivatives bearing respectively a pendant ethylenediamino (EDA) portion (HA-EDA) and both EDA and octadecyl pendant groups (HA-EDA-C18) were crosslinked through an azo-Michael reaction with INU-DV. Gelation time and consumption of DV portions have been evaluated on hydrogel obtained using HA-EDA and HA-EDA-C18 derivatives with a concentration of 3% w/v and a ratio 80/20 w/w respect to the crosslinker INU-DV. The presence of pendant C18 chains improves mechanical performances of hydrogels and decreases the susceptibility to hyaluronidase hydrolysis. Bovine chondrocytes, encapsulated during crosslinking, sufficiently survive and efficiently proliferate until 28 days of analysis.

  5. Synthesis, structure and cytotoxic activity of acetylenic derivatives of betulonic and betulinic acids

    Science.gov (United States)

    Bębenek, Ewa; Chrobak, Elwira; Wietrzyk, Joanna; Kadela, Monika; Chrobak, Artur; Kusz, Joachim; Książek, Maria; Jastrzębska, Maria; Boryczka, Stanisław

    2016-02-01

    A series of acetylenic derivatives of betulonic and betulinic acids has been synthesized and characterized by 1H and 13C NMR, IR and MS spectroscopy. The structure of propargyl betulonate 4 and propargyl betulinate-DMF solvate 8A was solved by X-ray diffraction. Thermal properties were examined using a DSC technique. The resulting alkynyl derivatives, as well as betulin 1 and betulinic acid 3, were evaluated in vitro for their cytotoxic activity against human T47D breast cancer, CCRF/CEM leukemia, SW707 colorectal, murine P388 leukemia and BALB3T3 normal fibroblasts cell lines. Several of the obtained compounds have a favorable cytotoxic profile than betulin 1. Propargyl betulinate 8 was the most active derivative, being up to 3-fold more potent than betulin 1 against the human leukemia (CCRF/CEM) cell line, with an IC50 value of 3.9 μg/mL.

  6. Enhanced lignin monomer production caused by cinnamic Acid and its hydroxylated derivatives inhibits soybean root growth.

    Directory of Open Access Journals (Sweden)

    Rogério Barbosa Lima

    Full Text Available Cinnamic acid and its hydroxylated derivatives (p-coumaric, caffeic, ferulic and sinapic acids are known allelochemicals that affect the seed germination and root growth of many plant species. Recent studies have indicated that the reduction of root growth by these allelochemicals is associated with premature cell wall lignification. We hypothesized that an influx of these compounds into the phenylpropanoid pathway increases the lignin monomer content and reduces the root growth. To confirm this hypothesis, we evaluated the effects of cinnamic, p-coumaric, caffeic, ferulic and sinapic acids on soybean root growth, lignin and the composition of p-hydroxyphenyl (H, guaiacyl (G and syringyl (S monomers. To this end, three-day-old seedlings were cultivated in nutrient solution with or without allelochemical (or selective enzymatic inhibitors of the phenylpropanoid pathway in a growth chamber for 24 h. In general, the results showed that 1 cinnamic, p-coumaric, caffeic and ferulic acids reduced root growth and increased lignin content; 2 cinnamic and p-coumaric acids increased p-hydroxyphenyl (H monomer content, whereas p-coumaric, caffeic and ferulic acids increased guaiacyl (G content, and sinapic acid increased sinapyl (S content; 3 when applied in conjunction with piperonylic acid (PIP, an inhibitor of the cinnamate 4-hydroxylase, C4H, cinnamic acid reduced H, G and S contents; and 4 when applied in conjunction with 3,4-(methylenedioxycinnamic acid (MDCA, an inhibitor of the 4-coumarate:CoA ligase, 4CL, p-coumaric acid reduced H, G and S contents, whereas caffeic, ferulic and sinapic acids reduced G and S contents. These results confirm our hypothesis that exogenously applied allelochemicals are channeled into the phenylpropanoid pathway causing excessive production of lignin and its main monomers. By consequence, an enhanced stiffening of the cell wall restricts soybean root growth.

  7. RNA:DNA Ratio and Other Nucleic Acid Derived Indices in Marine Ecology

    Directory of Open Access Journals (Sweden)

    Luis Chícharo

    2008-08-01

    Full Text Available Some of most used indicators in marine ecology are nucleic acid-derived indices. They can be divided by target levels in three groups: 1 at the organism level as ecophysiologic indicators, indicators such as RNA:DNA ratios, DNA:dry weight and RNA:protein, 2 at the population level, indicators such as growth rate, starvation incidence or fisheries impact indicators, and 3 at the community level, indicators such as trophic interactions, exergy indices and prey identification. The nucleic acids derived indices, especially RNA:DNA ratio, have been applied with success as indicators of nutritional condition, well been and growth in marine organisms. They are also useful as indicators of natural or anthropogenic impacts in marine population and communities, such as upwelling or dredge fisheries, respectively. They can help in understanding important issues of marine ecology such as trophic interactions in marine environment, fish and invertebrate recruitment failure and biodiversity changes, without laborious work of counting, measuring and identification of small marine organisms. Besides the objective of integrate nucleic acid derived indices across levels of organization, the paper will also include a general characterization of most used nucleic acid derived indices in marine ecology and also advantages and limitations of them. We can conclude that using indicators, such RNA:DNA ratios and other nucleic acids derived indices concomitantly with organism and ecosystems measures of responses to climate change (distribution, abundance, activity, metabolic rate, survival will allow for the development of more rigorous and realistic predictions of the effects of anthropogenic climate change on marine systems.

  8. Gd-DOTA: Preliminary pharmacologic results of a new contrast agent in MR

    International Nuclear Information System (INIS)

    Gd-DOTA is the most stable complex of gadolinium known at present. Its physico-chemical and toxicologic properties are compatible with future in vivo use (stability: K = 10/sup 28/; relaxivity R1 (270 MHz) = 3.5 mmol/sup -1/ . sec/sup -1/, LD50 when injected intravenously into mice = 11 mmol . kg/sup -1/). A crossover experiment conducted in 18 rabbits and six dogs injected intravenously with Gd-DOTA meglumine or Gd-DTPA dimeglumine showed no statistical difference in elimination parameters with variations in injected doses (0.1 mmol . kg/sup -1/ and 0.5 mmol . kg/sup -1/), species, or products. No target organ has been found, and the two products are rapidly eliminated almost exclusively by the kidney. Gd-DOTA appears to be a safe potential MR imaging contrast agent

  9. 韩国能否改变DOTA2格局?

    Institute of Scientific and Technical Information of China (English)

    尼博

    2013-01-01

    在世界电竞格局中,韩国一直是位列前茅的电竞强国。从最初的SC,到后来的War3,再到如今的SC2与LOL,韩国人在各个电竞项目中都取得了惊人的成就。随着DOTA2的来临,韩国已经正式进军DOTA2,在不久的将来,韩国人必将在DOTA2中掀起一阵血雨腥风。

  10. Uptake kinetics of the somatostatin receptor ligand [86Y]DOTA-dPhe1-Tyr3-octreotide ([86Y]SMT487) using positron emission tomography in non-human primates and calculation of radiation doses of the 90Y-labelled analogue

    International Nuclear Information System (INIS)

    [90Y]DOTA-dPhe1-Tyr3-octreotide ([90Y]-SMT487) has been suggested as a promising radiotherapeutic agent for somatostatin receptor-expressing tumours. In order to quantify the in vivo parameters of this compound and the radiation doses delivered to healthy organs, the analogue [86Y]DOTA-dPhe1-Tyr3-octreotide was synthesised and its uptake measured in baboons using positron emission tomography (PET). [86Y]DOTA-dPhe1-Tyr3-octreotide was administered at two different peptide concentrations, namely 2 and 100 μg peptide per m2 body surface. The latter concentration corresponded to a radiotherapeutic dose. In a third protocol [86Y]DOTA-dPhe1-Tyr3-octreotide was injected in conjunction with a simultaneous infusion of an amino acid solution that was high in l-lysine in order to lower the renal uptake of radioyttrium. Quantitative whole-body PET scans were recorded to measure the uptake kinetics for kidneys, liver, lung and bone. The individual absolute uptake kinetics were used to calculate the radiation doses for [90Y]DOTA-dPhe1-Tyr3-octreotide according to the MIRD recommendations extrapolated to a 70-kg human. The highest radiation dose was received by the kidneys, with 2.1-3.3 mGy per MBq [90Y]DOTA-dPhe1-Tyr3-octreotide injected. For the 100 μg/m2 SMT487 protocol with amino acid co-infusion this dose was about 20%-40% lower than for the other two treatment protocols. The liver and the red bone marrow received doses ranging from 0.32 to 0.53 mGy and 0.03 to 0.07 mGy per MBq [90Y]DOTA-dPhe1-Tyr3-octreotide, respectively. The average effective dose equivalent amounted to 0.23-0.32 mSv/MBq. The comparatively low estimated radiation doses to normal organs support the initiation of clinical phase I trials with [90Y]DOTA-dPhe1-Tyr3-octreotide in patients with somatostatin receptor-expressing tumours. (orig.)

  11. Potential biological applications of bio-based anacardic acids and their derivatives.

    Science.gov (United States)

    Hamad, Fatma B; Mubofu, Egid B

    2015-01-01

    Cashew nut shells (CNS), which are agro wastes from cashew nut processing factories, have proven to be among the most versatile bio-based renewable materials in the search for functional materials and chemicals from renewable resources. CNS are produced in the cashew nut processing process as waste, but they contain cashew nut shell liquid (CNSL) up to about 30-35 wt. % of the nut shell weight depending on the method of extraction. CNSL is a mixture of anacardic acid, cardanol, cardol, and methyl cardol, and the structures of these phenols offer opportunities for the development of diverse products. For anacardic acid, the combination of phenolic, carboxylic, and a 15-carbon alkyl side chain functional group makes it attractive in biological applications or as a synthon for the synthesis of a multitude of bioactive compounds. Anacardic acid, which is about 65% of a CNSL mixture, can be extracted from the agro waste. This shows that CNS waste can be used to extract useful chemicals and thus provide alternative green sources of chemicals, apart from relying only on the otherwise declining petroleum based sources. This paper reviews the potential of anacardic acids and their semi-synthetic derivatives for antibacterial, antitumor, and antioxidant activities. The review focuses on natural anacardic acids from CNS and other plants and their semi-synthetic derivatives as possible lead compounds in medicine. In addition, the use of anacardic acid as a starting material for the synthesis of various biologically active compounds and complexes is reported. PMID:25894225

  12. Potential Biological Applications of Bio-Based Anacardic Acids and Their Derivatives

    Directory of Open Access Journals (Sweden)

    Fatma B. Hamad

    2015-04-01

    Full Text Available Cashew nut shells (CNS, which are agro wastes from cashew nut processing factories, have proven to be among the most versatile bio-based renewable materials in the search for functional materials and chemicals from renewable resources. CNS are produced in the cashew nut processing process as waste, but they contain cashew nut shell liquid (CNSL up to about 30–35 wt. % of the nut shell weight depending on the method of extraction. CNSL is a mixture of anacardic acid, cardanol, cardol, and methyl cardol, and the structures of these phenols offer opportunities for the development of diverse products. For anacardic acid, the combination of phenolic, carboxylic, and a 15-carbon alkyl side chain functional group makes it attractive in biological applications or as a synthon for the synthesis of a multitude of bioactive compounds. Anacardic acid, which is about 65% of a CNSL mixture, can be extracted from the agro waste. This shows that CNS waste can be used to extract useful chemicals and thus provide alternative green sources of chemicals, apart from relying only on the otherwise declining petroleum based sources. This paper reviews the potential of anacardic acids and their semi-synthetic derivatives for antibacterial, antitumor, and antioxidant activities. The review focuses on natural anacardic acids from CNS and other plants and their semi-synthetic derivatives as possible lead compounds in medicine. In addition, the use of anacardic acid as a starting material for the synthesis of various biologically active compounds and complexes is reported.

  13. Comparison of sequential planar {sup 177}Lu-DOTA-TATE dosimetry scans with {sup 68}Ga-DOTA-TATE PET/CT images in patients with metastasized neuroendocrine tumours undergoing peptide receptor radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Sainz-Esteban, Aurora; Carril, Jose Manuel [Hospital Universitario Marques de Valdecilla, Department of Nuclear Medicine, Santander (Spain); Prasad, Vikas; Schuchardt, Christiane; Zachert, Carolin; Baum, Richard P. [Zentralklinik Bad Berka, Department of Nuclear Medicine and Centre for PET/CT, Bad Berka (Germany)

    2012-03-15

    The aim of the study was to compare sequential {sup 177}Lu-DOTA-TATE planar scans ({sup 177}Lu-DOTA-TATE) in patients with metastasized neuroendocrine tumours (NET) acquired during peptide receptor radionuclide therapy (PRRT) for dosimetry purposes with the pre-therapeutic {sup 68}Ga-DOTA-TATE positron emission tomography (PET)/CT ({sup 68}Ga-DOTA-TATE) maximum intensity projection (MIP) images obtained in the same patients concerning the sensitivity of the different methods. A total of 44 patients (59 {+-} 11 years old) with biopsy-proven NET underwent {sup 68}Ga-DOTA-TATE and {sup 177}Lu-DOTA-TATE imaging within 7.9 {+-} 7.5 days between the two examinations. {sup 177}Lu-DOTA-TATE planar images were acquired at 0.5, 2, 24, 48 and 72 h post-injection; lesions were given a score from 0 to 4 depending on the uptake of the radiopharmaceutical (0 being lowest and 4 highest). The number of tumour lesions which were identified on {sup 177}Lu-DOTA-TATE scans (in relation to the acquisition time after injection of the therapeutic dose as well as with regard to the body region) was compared to those detected on {sup 68}Ga-DOTA-TATE studies obtained before PRRT. A total of 318 lesions were detected; 280 (88%) lesions were concordant. Among the discordant lesions, 29 were {sup 68}Ga-DOTA-TATE positive and {sup 177}Lu-DOTA-TATE negative, whereas 9 were {sup 68}Ga-DOTA-TATE negative and {sup 177}Lu-DOTA-TATE positive. The sensitivity, positive predictive value and accuracy for {sup 177}Lu-DOTA-TATE as compared to {sup 68}Ga-DOTA-TATE were 91, 97 and 88%, respectively. Significantly more lesions were seen on the delayed (72 h) {sup 177}Lu-DOTA-TATE images (91%) as compared to the immediate (30 min) images (68%). The highest concordance was observed for bone metastases (97%) and the lowest for head/neck lesions (75%). Concordant lesions (n = 77; mean size 3.8 cm) were significantly larger than discordant lesions (n = 38; mean size 1.6 cm) (p < 0.05). No such significance was

  14. Gastroprotective Mechanisms of Action of Semisynthetic Carnosic Acid Derivatives in Human Cells

    Directory of Open Access Journals (Sweden)

    Cristina Theoduloz

    2014-01-01

    Full Text Available Carnosic acid (CA and its semisynthetic derivatives display relevant gastroprotective effects on HCl/ethanol induced gastric lesions in mice. However, little is known on the mechanisms of action of the new compounds. The aim of the present work was to assess the gastroprotective action mechanisms of CA and its derivatives using human cell culture models. A human gastric adenocarcinoma cell line (AGS and lung fibroblasts (MRC-5 were used to reveal the possible mechanisms involved. The ability of the compounds to protect cells against sodium taurocholate (NaT-induced damage, and to increase the cellular reduced glutathione (GSH and prostaglandin E2 (PGE2 content was determined using AGS cells. Stimulation of cell proliferation was studied employing MRC-5 fibroblasts. Carnosic acid and its derivatives 10–18 raised GSH levels in AGS cells. While CA did not increase the PGE2 content in AGS cells, all derivatives significantly stimulated PGE2 synthesis, the best effect being found for the 12-O-indolebutyrylmethylcarnosate 13. A significant increase in MRC-5 fibroblast proliferation was observed for the derivatives 7 and 16–18. The antioxidant effect of the compounds was assessed by the inhibition of lipid peroxidation in human erythrocyte membranes, scavenging of superoxide anion and DPPH discoloration assay. The new CA derivatives showed gastroprotective effects by different mechanisms, including protection against cell damage induced by NaT, increase in GSH content, stimulation of PGE2 synthesis and cell proliferation.

  15. Effect of root derived organic acids on the activation of nutrients in the rhizosphere soil

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Four types of soils, including brown coniferous forest soil, dark brown soil, black soil, and black calic soil, sampled from three different places in northeast China were used in this test. The functions of two root-derived organic acids and water were simulated and compared in the activation of mineral nutrients from the rhizosphere soil. The results showed that the organic acids could activate the nutrients and the activated degree of the nutrient elements highly depended on the amount and types of the organic acid excreted and on the physiochemical and biochemical properties of the soil tested. The activation effect of the citric acid was obviously higher than that of malic acid in extracting Fe, Mn, Cu, and Zn for all the tested soil types. However, the activation efficiencies of P, K, Ca, and Mg extracting by the citric acid were not much higher, sometimes even lower, than those by malic acid. The solution concentration of all elements increased with increase of amount of the citric acid added.

  16. Pantothenic acid and its derivatives protect Ehrlich ascites tumor cells against lipid peroxidation.

    Science.gov (United States)

    Slyshenkov, V S; Rakowska, M; Moiseenok, A G; Wojtczak, L

    1995-12-01

    Preincubation of Ehrlich ascites tumor cells at 22 or 32 degrees C, but not at 0 degree C, with pantothenic acid, 4'-phosphopantothenic acid, pantothenol, or pantethine reduced lipid peroxidation (measured by production of thiobarbituric acid-reactive compounds) induced by the Fenton reaction (Fe2+ + H2O2) and partly protected the plasma membrane against the leakiness to cytoplasmic proteins produced by the same reagent. Pantothenic acid and its derivatives did not inhibit (Fe2+ + H2O2)-induced peroxidation of phospholipid multilamellar vesicles, thus indicating that their effect on the cells was not due to the scavenging mechanism. Homopantothenic acid and its 4'-phosphate ester (which are not precursors of CoA) neither protected Ehrlich ascites tumor cells against lipid peroxidation nor prevented plasma membrane leakiness under the same conditions. Incubation of the cells with pantothenic acid, 4'-phosphopantothenic acid, pantothenol, or pantethine significantly increased the amount of cellular CoA and potentiated incorporation of added palmitate into phospholipids and cholesterol esters. It is concluded that pantothenic acid and its related compounds protect the plasma membrane of Ehrlich ascites tumor cells against the damage by oxygen free radicals due to increasing cellular level of CoA. The latter compound may act by diminishing propagation of lipid peroxidation and promoting repair mechanisms, mainly the synthesis of phospholipids. PMID:8582649

  17. Syntheses,characteristics and fluorescence properties of complexes of terbium with benzoic acid and its derivatives

    Institute of Scientific and Technical Information of China (English)

    ZHOU Zhong-cheng; SHU Wan-gen; RUAN Jian-ming; HUANG Bai-yun; LIU You-nian

    2005-01-01

    The binary complexes of terbium with benzoic acid and its derivatives (phthalic acid,iso-phthalic acid,oaminobenzoic acid,salicylic acid,sulfosalicylic acid) were synthesized and their compositions were identified by elemental analyses.UV,IR of the complexes were investigated.The UV spectra indicate that the complexes'ultraviolet absorption is mainly the ligands' absorption,but the location of peak drifts.The IR spectra show that the IR spectra of complexes are different from those of free ligands,and the band at 400-500 cm-1,due to the stretching vibration of Tb-O,is absent for free ligands.The fluorescence properties were investigated by using luminescence spectroscope,the results show that all the six complexes of terbium exhibit excellent luminescence,due to the transition from the lowest excited state 5D4 to 7F ground state manifold,the complexes of terbium with sulfosalicylic acid have the strongest fluorescence intensity,and is stronger than o-aminobenzoic acid-terbium,whose fluorescence intensity is regarded as the strongest one in the literature,and even stronger than some phosphor of terbium.

  18. Enzymatic synthesis of enantiopure alpha- and beta-amino acids by phenylalanine aminomutase-catalysed amination of cinnamic acid derivatives.

    Science.gov (United States)

    Wu, Bian; Szymanski, Wiktor; Wietzes, Piet; de Wildeman, Stefaan; Poelarends, Gerrit J; Feringa, Ben L; Janssen, Dick B

    2009-01-26

    The phenylalanine aminomutase (PAM) from Taxus chinensis catalyses the conversion of alpha-phenylalanine to beta-phenylalanine, an important step in the biosynthesis of the N-benzoyl phenylisoserinoyl side-chain of the anticancer drug taxol. Mechanistic studies on PAM have suggested that (E)-cinnamic acid is an intermediate in the mutase reaction and that it can be released from the enzyme's active site. Here we describe a novel synthetic strategy that is based on the finding that ring-substituted (E)-cinnamic acids can serve as a substrate in PAM-catalysed ammonia addition reactions for the biocatalytic production of several important beta-amino acids. The enzyme has a broad substrate range and a high enantioselectivity with cinnamic acid derivatives; this allows the synthesis of several non-natural aromatic alpha- and beta-amino acids in excellent enantiomeric excess (ee >99 %). The internal 5-methylene-3,5-dihydroimidazol-4-one (MIO) cofactor is essential for the PAM-catalysed amination reactions. The regioselectivity of amination reactions was influenced by the nature of the ring substituent.

  19. [Study of early myocardial infarction by nuclear magnetic resonance imaging with gadolinium Dota injection].

    Science.gov (United States)

    Jau, P; Bonnet, J L; Joly, P; Barth, P; Habib, G; Djiane, P; Bory, M; Bernard, P J

    1991-02-01

    Ten patients with acute myocardial infarction were studied by magnetic resonance imaging (MRI) with injection of a paramagnetic contrast agent: Gadolinium-DOTA (Gd-DOTA). The time interval between the onset of symptoms and MRI was 8 to 12 days. The site of infarction was determined in all cases by Thallium 201 scintigraphy (hypofixation) and selective ventriculography (segmental wall anomalies): anterior (6 cases), inferior (4 cases). MRI was performed with a 0.5 Tesla CGR Magniscan by the multiple spin technique. A series of tomographic sections was recorded immediately after intravenous injection of 0.4 mmol/Kg of Gd-DOTA. Recent myocardial infarction with parenchymal oedema gives an enhanced transmural signal: only 3 patients had a sufficiently contrasted image on the 1st spin echo. After Gd-DOTA, 7 patients had significantly increased contrast on this echo and in all excellent contrast between infarcted and healthy myocardium was obtained in 9 of the 10 patients. There was excellent correlation concerning the site of infarction between Thallium scintigraphy and left ventriculography. The intensity of signal and T2 relaxation time of different myocardial segments was studied by the regions of interest technique: the ratio of signal intensity of infarcted/healthy myocardium was 1.3 before and 1.7 after Gd-DOTA on first spin echo images. The mean T2 was 54.1 +/- 9 ms in healthy and 82 +/- 28 ms in infarcted myocardium. After Gd-DOTA, both values decreased and tended to equalize.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Synthesis of 2-phenyl- and 2,3-diphenyl-quinolin-4-carboxylic acid derivatives

    International Nuclear Information System (INIS)

    Quinolin derivatives are a group of compounds known to possess a wide range of biological activities. The chemistry of quinolines together with their corresponding aldehydes were dealt with in chapter one of this study. Special emphasis was given to the chemistry of benzaldehyde. Twenty five 2-phenyl- and 2,3-diphenyl-quinolin-4-carboxylic acid derivatives together with their corresponding intermediates were prepared in this work. Basically, the synthetic design of these compounds arise from the appropriate disconnections of the target 2-phenyl and 2,3-diphenyl-quinolin-4-carboxylic acids. The retro synthesis analysis of these compounds reveals pyruvic acid, aromatic amine and benzaldehyde or phenyl pyruvic acid, aromatic amine and benzaldehyde as possible logical precursors for 2-phenyl-and 2,3-diphenyl- quinoline-4-carboxylic acids respectively. The purity and identities of the synthesized compounds were elucidated through chromatographic and spectroscopic techniques. The compounds were heavily subjected to spectroscopic analysis (UV, IR, GC/MS, 1H-and 13C- NMR). The appropriate disconnections and the mechanisms of the corresponding reactions were given and discussed in chapter three. The spectral data were interpreted and correlated with the target structures. The prepared 2-phenyl- and 2,3-diphenyl-quinoline-4-carboxylic acid derivatives were screened for their antibacterial activity. The compounds were tested against the standard bacterial organisms B. subtilis, S. aureus, E. coli and P. vulgaris. Some of these compounds were devoid of antibacterial activity against S. aureus and P. vulgaris, while others showed moderate activity. All of the tested compounds showed an activity against B. subtilis and E. coli. 2,3-diphenyl -6-sulphanilamide-quinolin-4-carboxylic acid showed the highest activity against the four standard tested organisms.(Author)

  1. Modeling of biodistribution of 90 Y-DOTA-hR3 by using artificial intelligence techniques

    International Nuclear Information System (INIS)

    In this work the biodistribution of radioimmunoconjugate 90Y-DOTA-hR3 was modeled by using an artificial neural network. In vivo stability of 90Y-DOTA-hR3 was determined in healthy male Wistar rats at 4, 24 and 48 hours, in different organs. A model describing the relationship between, by one hand, the incorporated dose and, by the other hand, organ and time was developed by using a multilayer perceptron neural network. Adjusted model was analyzed by several statistical tests. Outcomes shown that proposed neural model describes the relationship between the studied variables in a proper way. (Author)

  2. Extraction of gold, palladium, and platinum from acidic media with cyclic sulfoxide derivative

    Institute of Scientific and Technical Information of China (English)

    Songping Wu; Guobang Gu

    2007-01-01

    The extraction of gold (Ⅲ), palladium (Ⅱ), and platinum (Ⅳ) from the acidic media with the cyclic sulfoxide derivative of a-dodecyl-tetrahydrothiophene 1-oxide (dtmso) was investigated. Gold (Ⅲ), palladium (Ⅱ), and platinum (Ⅳ) could be separated from the acidic media with suitable sulfoxide concentration and acidity. The extraction reaction of gold (Ⅲ), palladium (Ⅱ) or platinum (Ⅳ) is exothermic when dtmso is used as an extracting reagent. The coordination number was studied by the slope method. The results indicate that, in high acidity, the dtmso coordination number for extracting gold (Ⅲ) or palladium (Ⅱ) is 3, and that for platinum (Ⅳ) is 2. UV and FT-IR spectra were used to analyze the structure of the complex. Gold (Ⅲ) is coordinated with the oxygen atom in S=O group in dtmso, and palladium (Ⅱ) or platinum (Ⅳ) is coordinated with the sulfur atom in S=O group in dtmso.

  3. MOF-Derived Tungstated Zirconia as Strong Solid Acids toward High Catalytic Performance for Acetalization.

    Science.gov (United States)

    Wang, Peng; Feng, Jian; Zhao, Yupei; Wang, Shaobin; Liu, Jian

    2016-09-14

    A strong solid acid, tungstated zirconia (WZ), has been prepared first using tungstate immobilized UiO-66 as precursors through a "double-solvent" impregnation method under mild calcination temperature. With moderate W contents, the as-synthesized WZ catalysts possess a high density of acid sites, and the proper heat treatment also has facilely led to a bunch of oligomeric tungsten clusters on stabilized tetragonal ZrO2. The resultant solid acids show an improved catalytic performance toward the benzaldehyde's acetalization in comparison with traditional zirconium hydroxide-prepared WZ. Notably, due to large surface area and additionally introduced strong acid sites, the MOF-derived WZ catalysts afforded conversion up to 86.0%. The facile method endows the WZ catalysts with superior catalytic activities and excellent recyclability, thus opening a new avenue for preparation of metal oxide-based solid superacids and superbases. PMID:27557351

  4. Chiral trans-1,2-diaminocyclohexane derivatives as chiral solvating agents for carboxylic acids

    Indian Academy of Sciences (India)

    Mariappan Periasamy; Manasi Dalai; Meduri Padmaja

    2010-07-01

    Efficient use of the readily accessible chiral 2-symmetric acyclic diamines (1-2) as well as macrocyclic amines (3-5) containing trans-1,2-diaminocyclohexyl moiety as chiral solvating agents (CSA) for the determination of enantiomeric excess of representative carboxylic acids (6-7) and an amino acid derivative (8) is illustrated. The enantiomeric composition of different carboxylic acids estimated here by the 1H NMR method, based on the integration of the corresponding methine proton signals are in good correlation with that determined using HPLC method. The data are in accordance with the formation of multimolecular diastereomeric complexes in solution, which render good splitting of NMR signals for the enantiomers of representative carboxylic acids as well as for -Ts-phenylglycine (up to = 0.295 ppm, 118 Hz).

  5. 2,5-PRODAN Derivatives as Highly Sensitive Sensors of Low Solvent Acidity

    Directory of Open Access Journals (Sweden)

    Alexandra H. Yoon

    2014-05-01

    Full Text Available Two 5-acyl-2-dimethylaminonaphthalene derivatives, one with a propionyl group and the other with a fused cyclohexanone ring, are investigated as sensors of H-bond-donating ability in protic solvents of low solvent acidity. Their fluorescence is highly quenched in protic solvents, and the quenching order of magnitude is linearly related to the H-bond-donating ability of the solvent as quantified by the solvent acidity (SA scale. As the solvent acidity increases from 0.15 to 0.40, the fluorescence for both is quenched by more than a factor of ten; thus, they are extremely sensitive sensors of the hydrogen-bond-donating ability in this weakly acidic range. Preferential solvation studies suggest that quenching occurs from a doubly H-bonded excited state.

  6. Two glucosylated abscisic acid derivates from avocado seeds (Persea americana Mill. Lauraceae cv. Hass).

    Science.gov (United States)

    del Refugio Ramos, María; Jerz, Gerold; Villanueva, Socorro; López-Dellamary, Fernando; Waibel, Reiner; Winterhalter, Peter

    2004-04-01

    Phytochemical investigation of avocado seed material (Persea americana Mill., Lauraceae) resulted in the isolation of two glucosylated abscisic acid derivates. One of these was not known as a natural product and can be regarded as a potential 'missing link' in abscisic acid metabolism in plants. After fractionation by high-speed countercurrent chromatography, and multiple steps of column chromatography, structures were elucidated by 1D-, 2D-NMR, electrospray-MS to be the novel beta-d-glucoside of (1'S,6'R)-8'-hydroxyabscisic acid, and (1'R,3'R,5'R,8'S)-epi-dihydrophaseic acid beta-d-glucoside. Absolute configuration was determined by circulardichroism, optical rotation, and by NOE experiments.

  7. Radiopharmacology of iminodiacetic acid N-derivatives analysis in biological models and comparison to human beings

    International Nuclear Information System (INIS)

    It was studied the influence of chemical structures and molecular weight in the distribution of several iminodiacetic acid N-derivatives and to determine the potential use of these radiopharmaceuticals in humans. The study was performed with the following derivatives: N-(2,6 dimetyphenylcarbamoylmethy) iminodiacetic acid, N(2.6 dietylphenyl-carbamoylmethy) iminodiacetic acid, N-(2,6 diisopropylphenylcarbamoylmethy) iminodiacetic acid and the previously unknown N-derivative N-(2,6 diisopropyl, phenylcarbamoylethyl) iminodiacetic aced. These were sinthesized by a modified procedure by MITTA et al. and controlled by NMR, mass spectrometry, elemental composition and also toxicity pirogens, lethal dose and the chelate's radiochemical dose were determined. Liver gallbladder, intestinal and renal kinetics were studied in mice. In order to evaluate the metabolic pathways of the radiopharmaceuticals, the content of gallbladder and the urine were reinjected. Plasma kinetics and the plasmatic half life was determined by extracorporeal circulation in Wistar rats. For the use in human beings, test were carried out in different branches of nuclear medicine, in normal volunteers and carriers of different pathologic disorders. The patients were divided into four groups: acute and chronic cholecystitis, cirrhosis and jaundice. It was obtained the liver/heart activity ratio and estimated the appearance times of the intrahepatic ducts, gallbladder, duodenum and renal persistence. (M.E.L.)

  8. Effect of vanillin and its acid and alcohol derivatives on the diphenolase activity of mushroom tyrosinase

    Directory of Open Access Journals (Sweden)

    Masoomeh Bagheri-Kalmarzi

    2012-01-01

    Full Text Available For the first time in the present study the effects of vanillin, vanillyl alcohol, vanillic acid, as well as the newly synthesized vanillin derivative, bis-vanillin, were investigated on the oxidation of dopamine hydrochloride by mushroom tyrosinase. Among them, vanillin and bis-vanillin act as activators, while vanillyl alcohol and vanillic acid exhibited inhibitory effects, the IC50 values being estimated 1.5 and 1.0 mM, respectively. These compounds were mixed inhibitors. The presence of aldehyde and metoxy groups at the meta position of aromatic compounds seems to cause them to react as tyrosinase activators, as observed in the case of vanillin and bis-vanillin. The presence of both groups in bis-vanillin results in a stronger activation effect compared to vanillin. The results indicate that the electron-withdrawing capacity of the functional group at the C-1 position is essential for the inhibitory potency of vanillin derivatives. In comparison with other benzoic acid derivatives, the results obtained in this study suggest that the relative positioning of hydroxy and methoxy groups at meta and para positions plays an important role in the inhibition effects of benzoic acids and their inhibition potency.

  9. Carboxylic Acid Fullerene (C60) Derivatives Attenuated Neuroinflammatory Responses by Modulating Mitochondrial Dynamics

    Science.gov (United States)

    Ye, Shefang; Zhou, Tong; Cheng, Keman; Chen, Mingliang; Wang, Yange; Jiang, Yuanqin; Yang, Peiyan

    2015-05-01

    Fullerene (C60) derivatives, a unique class of compounds with potent antioxidant properties, have been reported to exert a wide variety of biological activities including neuroprotective properties. Mitochondrial dynamics are an important constituent of cellular quality control and function, and an imbalance of the dynamics eventually leads to mitochondria disruption and cell dysfunctions. This study aimed to assess the effects of carboxylic acid C60 derivatives (C60-COOH) on mitochondrial dynamics and elucidate its associated mechanisms in lipopolysaccharide (LPS)-stimulated BV-2 microglial cell model. Using a cell-based functional screening system labeled with DsRed2-mito in BV-2 cells, we showed that LPS stimulation led to excessive mitochondrial fission, increased mitochondrial localization of dynamin-related protein 1 (Drp1), both of which were markedly suppressed by C60-COOH pretreatment. LPS-induced mitochondria reactive oxygen species (ROS) generation and collapse of mitochondrial membrane potential (Δ Ψm) were also significantly inhibited by C60-COOH. Moreover, we also found that C60-COOH pretreatment resulted in the attenuation of LPS-mediated activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling, as well as the production of pro-inflammatory mediators. Taken together, these findings demonstrated that carboxylic acid C60 derivatives may exert neuroprotective effects through regulating mitochondrial dynamics and functions in microglial cells, thus providing novel insights into the mechanisms of the neuroprotective properties of carboxylic acid C60 derivatives.

  10. The influence of humic acids derived from earthworm-processed organic wastes on plant growth

    Energy Technology Data Exchange (ETDEWEB)

    Atiyeh, R.M.; Lee, S.; Edwards, C.A.; Arancon, N.Q.; Metzger, J.D. [Ohio State University, Columbus, OH (United States). Soil Ecology Lab.

    2002-08-01

    Some effects of humic acids, formed during the breakdown of organic wastes by earthworms (vermicomposting), on plant growth were evaluated. In the first experiment, humic acids were extracted from pig manure vermicompost using the classic alkali/acid fractionation procedure and mixed with a soilless container medium (Metro-Mix 360), to provide a range of 0, 50, 100, 150, 200, 250, 500, 1000, 2000 and 4000 mg of humate per kg of dry weight of container medium, and tomato seedlings were grown in the mixtures. In the second experiment, humates extracted from pig manure and food wastes vermicomposts were mixed with vermiculite to provide a range of 0, 50, 125, 250, 500, 1000 and 4000 mg of humate per kg of dry weight of the container medium, and cucumber seedlings were grown in the mixtures. Both tomato and cucumber seedlings were watered daily with a solution containing all nutrients required to ensure that any differences in growth responses were not nutrient-mediated. The incorporation of both types of vermicompost-derived humic acids, into either type of soilless plant growth media, increased the growth of tomato and cucumber plants significantly, in terms of plant heights, leaf areas, shoot and root dry weights. Plant growth increased with increasing concentrations of humic acids incorporated into the medium up to a certain proportion, but this differed according to the plant species, the source of the vermicompost, and the nature of the container medium. Plant growth tended to be increased by treatments of the plants with 50-500 mg/kg humic acids, but often decreased significantly when the concentrations of humic acids derived in the container medium exceeded 500-1000 mg/kg. These growth responses were most probably due to hormone-like activity of humic acids from the vermicomposts or could have been due to plant growth hormones adsorbed onto the humates. (author)

  11. Evaluation of 177Lu-DOTA-labeled aglycosylated monoclonal anti-L1-CAM antibody chCE7: influence of the number of chelators on the in vitro and in vivo properties

    International Nuclear Information System (INIS)

    Introduction: In this study, we optimized the 1,4,7,10-tetraazacyclododecane-N-N'-N''-N''''-tetraacetic acid (DOTA) chelator-to-antibody (c/a) ratio for the aglycosylated variant of the anti-L1-CAM antibody chCE7 (chCE7agl), providing high specific activity and low liver uptake in 177Lu-labeled form. Methods: chCE7agl was substituted with increasing molar excess of DOTA-NCS. The number of chelators coupled to the antibody and the binding affinities to target tumor cells (IC5 values) of the resulting immunoconjugates were determined. The different immunoconjugates were labeled with 177Lu; specific activity was measured, and metabolic stability was analyzed in human plasma. The effect of different c/a ratios on blood clearance and liver uptake was tested in nude mice. Changes of the protein backbone structure were analyzed by circular dichroism spectroscopy. Results: chCE7agl was substituted with 7, 12 or 15 DOTA ligands. The IC5 concentrations displacing radioiodinated chCE7 antibody increased with the number of chelators (1.5-fold with 7 ligands, 2.5-fold with 12 ligands and a 5-fold increase with 15 ligands). The highest specific activity for 177Lu-DOTA-chCE7agl was obtained with a c/a ratio of 12 (106 MBq/mg). Radioimmunoconjugates were stable in human plasma for at least 24 h. Blood clearance and liver uptake were measured after 24 h (c/a ratios of 12 and 15) or 48 h (c/a ratio of 7). The liver-to-blood ratios were 0.35±0.14 (7 ligands), 0.77±0.19 (12 ligands) and 17.85±3.44 (15 ligands). Conclusions: DOTA-chCE7agl conjugates with a c/a ratio of 12 combined high specific activity with good in vitro and in vivo properties. The rapid elimination rate from the blood and the high uptake in the liver of chCE7agl substituted with 15 DOTA ligands were found not to be due to conformational changes of the antibody backbone structure

  12. Highly efficient production of D-lactic acid from chicory-derived inulin by Lactobacillus bulgaricus.

    Science.gov (United States)

    Xu, Qianqian; Zang, Ying; Zhou, Jie; Liu, Peng; Li, Xin; Yong, Qiang; Ouyang, Jia

    2016-11-01

    Inulin is a readily available feedstock for cost-effective production of biochemicals. To date, several studies have explored the production of bioethanol, high-fructose syrup and fructooligosaccharide, but there are no studies regarding the production of D-lactic acid using inulin as a carbon source. In the present study, chicory-derived inulin was used for D-lactic acid biosynthesis by Lactobacillus bulgaricus CGMCC 1.6970. Compared with separate hydrolysis and fermentation processes, simultaneous saccharification and fermentation (SSF) has demonstrated the best performance of D-lactic acid production. Because it prevents fructose inhibition and promotes the complete hydrolysis of inulin, the highest D-lactic acid concentration (123.6 ± 0.9 g/L) with a yield of 97.9 % was obtained from 120 g/L inulin by SSF. Moreover, SSF by L. bulgaricus CGMCC 1.6970 offered another distinct advantage with respect to the higher optical purity of D-lactic acid (>99.9 %) and reduced number of residual sugars. The excellent performance of D-lactic acid production from inulin by SSF represents a high-yield method for D-lactic acid production from non-food grains. PMID:27440161

  13. Inclusion Behavior of Dimer b-Cyclodextrin Bridged with Aspartic Acid Derivative

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The b-cyclodextrin (CD) dimer bridged with aspartic acid (ASP) derivative, FITC-ASP(NH-b-CD)2 (Host, FITC=fluorescein-4-isothiocyanate), was synthesized. Fluorescence polarization study showed that the novel host formed an inclusion compound, [FITC-ASP(NH-b-CD)2]ATA, for which Kd was determined to be 5.0×10-6 mol/L by Beacon 2000 Analyzer, when ATA (Guest) = Adm-Trp-Arg-Arg-NH2 (Adm = 1-adamantanecarboxylic acid, Trp = tryptophan, Arg = arginine), where Kd is the dissociation constant in aqueous solution at 298 K.

  14. Synthesis of some salicylic acid derivatives and studies of their interaction with uranyl ion

    International Nuclear Information System (INIS)

    Some unsubstituted and substituted bis-derivatives of salicylic acid were synthesized and their acidity constants determined spectrophotometrically in 61.10% aqueous ethanol. The stability constants of complexes which these compounds form with the UO22+ ion were determined spectrophotometrically using the method of continuous variation under the following conditions: pH 3.58 and 3.98, 61.10% aqueous ethanol, μ=0.5 (LiCl), 25±1 degC. (author). 3 figs., 2 tabs., 8 refs

  15. Potential antibacterial activity of coumarin and coumarin-3-acetic acid derivatives.

    Science.gov (United States)

    Chattha, Fauzia Anjum; Munawar, Munawar Ali; Nisa, Mehrun; Ashraf, Mohammad; Kousar, Samina; Arshad, Shafia

    2015-05-01

    Coumarin and coumarin-3-acetic acid derivatives were synthesized by reacting phenols with malic acid, ethyl acetoacetate and ethyl acetylsuccinate in appropriate reaction conditions. All synthesized compounds were subjected to test for their antimicrobial activities against variety of gram positive (Bacillus subtilis, Staphylococcus aureus) and gram negative bacterial stains (Shigella sonnei, Escherichia coli) by agar dilution method. Several of them exhibited appreciable good antibacterial activity against the different strains of gram positive and gram negative bacteria. These findings suggest a great potential of these compounds for screening and use as antibacterial agents for further studies with a battery of bacteria.

  16. Preparation and evaluation of 177Lu-DOTA-Bz-RGD dimer and 177Lu-DOTA-Bz-PEG4-RGD dimer

    International Nuclear Information System (INIS)

    177Lu-DOTA-Bz-RGD dimer and 177Lu-DOTA-Bz-PEG4-RGD dimer were pre- pared, and the effect of PEG4 on labeling conditions and in vitro stability as well as pharma-cokinetic properties and biodistribution in normal mice for the radiolebeled compounds was compared. The results of TLC and HPLC show that the labeling yield of two radiolabeled compounds was more than 95% under optimal conditions (pH 4.0 and pH 6.0, respectively, reacting at 100 degree C for 15-20 min). The two radiolabeled compounds show pretty good stability in saline. HPLC analyses and lgPow values revealed that introducing of PEG4 increased the lipophilic character of radiolabeled compounds, but had no significant changes on pharmacokinetic properties and biodistribution in normal mice. (authors)

  17. A Benzoic Acid Derivative and Flavokawains from Piper species as Schistosomiasis Vector Controls

    Directory of Open Access Journals (Sweden)

    Ludmila N. Rapado

    2014-04-01

    Full Text Available The search of alternative compounds to control tropical diseases such as schistosomiasis has pointed to secondary metabolites derived from natural sources. Piper species are candidates in strategies to control the transmission of schistosomiasis due to their production of molluscicidal compounds. A new benzoic acid derivative and three flavokawains from Piper diospyrifolium, P. cumanense and P. gaudichaudianum displayed significant activities against Biomphalaria glabrata snails. Additionally, “in silico” studies were performed using docking assays and Molecular Interaction Fields to evaluate the physical-chemical differences among the compounds in order to characterize the observed activities of the test compounds against Biomphalaria glabrata snails.

  18. Phase Transfer Catalyzed Synthesis of Thiosemicarbazide Derivatives of 2-ethoxybenzoic Acid

    Institute of Scientific and Technical Information of China (English)

    WEI TaiBao; ZHANG YouMing; WU JiaWei

    2001-01-01

    @@ A series of 1,4-disubstitued thiosemicarbazides and their related heterocyclic compounds have been found to possess important biological activities[1]. Some thiosemicarbazides have been found to be useful as herbicides, insecticides and plant-growth regulators [1]. In view of these and in continuation of our earlier work on the synthesis and biological activity of thiosemicarbaides derivatives [2], we now report a convenient and efficient method for the preparation of thiosemicarbazides derivatives of 2-ethoxybenzoic acid under the condition of solid-liquid phase transfer catalysis using PEG-400 as the catalyst.

  19. Phase Transfer Catalyzed Synthesis of Thiosemicarbazide Derivatives of 2-ethoxybenzoic Acid

    Institute of Scientific and Technical Information of China (English)

    WEI; TaiBao

    2001-01-01

    A series of 1,4-disubstitued thiosemicarbazides and their related heterocyclic compounds have been found to possess important biological activities[1]. Some thiosemicarbazides have been found to be useful as herbicides, insecticides and plant-growth regulators [1]. In view of these and in continuation of our earlier work on the synthesis and biological activity of thiosemicarbaides derivatives [2], we now report a convenient and efficient method for the preparation of thiosemicarbazides derivatives of 2-ethoxybenzoic acid under the condition of solid-liquid phase transfer catalysis using PEG-400 as the catalyst.  ……

  20. The First General Electron Transfer Reductions of Carboxylic Acid Derivatives Using Samarium Diiodide

    OpenAIRE

    Spain, Malcolm Peter

    2014-01-01

    The development of new methods for the reduction of carboxylic acid derivatives is described. The ability to reduce these carbonyl derivatives through radical intermediates provides an orthogonal approach as compared with hydride based reductions.Initial experiments focused on the development of the SmI2–H2O system, where we have shown that chelation effects can be utilised to facilitate reduction of cyclic esters. Furthermore, a revised mechanism for the SmI2–H2O mediated reduction of lacton...

  1. Molecular markers derived from bombesin for tumor diagnosis by SPECT and PET

    International Nuclear Information System (INIS)

    A high number of molecules have already been identified to have high affinity to some receptors overexpressed on tumour cells and the radiolabelling of those molecules offers the possibility of new compounds for tumour diagnosis and therapy by nuclear medicine. Among of those molecules, bombesin (BBN) has become focus of interest, as its BB2 receptors are known to be overexpressed in prostate, breast, colon, pancreatic and lung tumour, as long as glioblastomas and neuroblastomas. BBN agonists and antagonists have already been described for this purpose and promising results were obtained in preclinical studies. However, most of them exhibited high abdominal accumulation, especially in pancreas and intestines, which can compromise diagnosis accuracy and cause serious adverse effects in therapy. In this context, the goal of the present work to radiolabel new BBN derivatives with 111In and 68Ga and to evaluate their potential for BB2 positive tumors diagnosis by single photon emission tomography (SPECT) and positron emission tomography (PET). The structure of studied peptides was Q-YGn-BBN(6-14), where Q is the chelator, n is the number of glycine aminoacids in the spacer YGn and BBN(6-14) is the original bombesin sequence from the aminoacid 6 to 14. The derivative in which the last aminoacid (methionine, Met) was replaced by norleucine (Nle) was also evaluated. The experimental evaluation of the bombesin derivatives was divided into four steps: computational studies, molecular markers for SPECT, molecular markers for PET and toxicological studies. The theoretical partition (log P) and distribution (log D) coefficients were calculated for all bombesin derivatives conjugated to DTPA (diethylenetriaminepentaacetic acid) and DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) chelators applying computational programmes. Bombesin derivatives for SPECT were developed by radiolabelling DTPA-conjugated bombesin derivatives with 111In to determine the best spacer

  2. Synthetic studies of coumarin derivatives from o-hydroxybenzophenones with phenylacetic acid and acetic anhydride

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Soon Hee; Yang, Sung Yun [Ewha Womans Univ., Seoul (Korea, Republic of)

    1999-02-01

    The 8 coumarin derivatives have been synthesized from 8 starting materials(2-hydroxy-benzophenone, 2,2'-dihydroxybenzophenone, 2,4-dihydroxybenzophenone, 2-hydroxy-5-methylbenzophenone, 5-chloro-2-hydroxy-4-methylbenzophenone, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-4'-dimethoxybenzophenone) with phenylacetic acid and Ac{sub 2}O/TEA in acetone at reflux temperature. The ratio of o-hydroxybenzophenone, phenylacetic acid, Ac{sub 2}O and TEA is 1:1:8:8 in acetone. Our results showed higher products yields of coumarin derivatives than Shama and Ray's method in previous papers. A new intermediate form was proposed to our mechanism of coumarin synthetic method.

  3. Lipid Peroxidation Inhibitation Activity of Maillard Reaction Products Derived from Sugar-amino Acid Model Systems

    Directory of Open Access Journals (Sweden)

    Nanjing Zhong

    2015-08-01

    Full Text Available The present study aimed to evaluate the lipid peroxidation inhibitation activity of Maillard Reaction Products (MRPs derived from sugar (glucose, fructose, lactose and maltose and 18 amino acid model systems in soybean oil. MRPs were produced by heating at 130°C for 2 h. Of the 18 amino acids-fructose model systems studied, MRPs derived from fructose-leucine, fructose-methionine, fructose-phenylalanine and fructose-isoleucine model sytems showed high lipid peroxidation inhibitation activity and best performance was observed from fructose-phenylalanine MRPs. Interestingly, glucose-phenylalanine MRPs also exhibited high inhibitation activity and inhibitation activity of both glucose-phenylalanine and fructose-phenylalanine MRPs exceeded 87% even with concentration at 1.1 wt % after 8 days storage.

  4. N-heterocyclic Amine Derivatives as Efficient Corrosion Inhibitors for Carbon Steel in Acidic Medium

    International Nuclear Information System (INIS)

    A novel heterocyclic amine derivatives, namely N, N'-substituted pyridinyl ethylene diamine tetra acetic acid sodium salt (A) and ethylene diamine N, N'-diacetic acid di (2-methylene tetra hydro furfuryl) acetate (B) were synthesized and their structure confirmations were performed by FTIR, HNMR and CNMR spectra. The inhibition effectiveness was evaluated against the corrosion of carbon steel in 1 M HCl by weight loss and polarization techniques. The results showed that the synthesized derivatives are good corrosion inhibitors for carbon steel in 1 M HCl medium, their inhibition efficiency, increased with inhibitor concentration, and (A) is slightly more effective than (B). The potentiostatic polarization study showed that (A) and (B) are mixed-type inhibitors in 1 M HCl. These compounds prevent carbon steel from corrosion by adsorption to the steel surface and forming insoluble complexes with ferrous species. The weight loss results and potentiostatic polarization studies were in reasonable agreement. (author)

  5. HPLC Enantioseparation of Phenylcarbamic Acid Derivatives by Using Macrocyclic Chiral Stationary Phases

    Directory of Open Access Journals (Sweden)

    Hroboňová Katarína

    2016-06-01

    Full Text Available The HPLC by using chiral stationary phases based on macrocyclic antibiotics, dimethylphenyl carbamate cyklofructan 7 and β-cyclodextrin in terms of polar-organic separation mode (mobile phase methanol/acetonitrile/acetic acid/triethylamine were used for enantioseparation of alkoxy derivatives of phenylcarbamic acid. The effect of the analyte structures on the efficiency of enantioseparation was investigated. The most suitable stationary phase was teicoplanin aglycone, where the separations of the enantiomers were obtained (the resolution value from 0.65 to 2.90, depending on the structure of the analyte. Significant effect on the resolution of the enantiomers has position of alkoxy substituent in the hydrophobic part of the molecule. The enantiorecognition was achieved for 3-alkoxysubstituted derivatives.

  6. Stereoselective Synthesis of α-Amino-C-phosphinic Acids and Derivatives

    Directory of Open Access Journals (Sweden)

    José Luis Viveros-Ceballos

    2016-08-01

    Full Text Available α-Amino-C-phosphinic acids and derivatives are an important group of compounds of synthetic and medicinal interest and particular attention has been dedicated to their stereoselective synthesis in recent years. Among these, phosphinic pseudopeptides have acquired pharmacological importance in influencing physiologic and pathologic processes, primarily acting as inhibitors for proteolytic enzymes where molecular stereochemistry has proven to be critical. This review summarizes the latest developments in the asymmetric synthesis of acyclic and phosphacyclic α-amino-C-phosphinic acids and derivatives, following in the first case an order according to the strategy used, whereas for cyclic compounds the nitrogen embedding in the heterocyclic core is considered. In addition selected examples of pharmacological implications of title compounds are also disclosed.

  7. Fast repair of oxidizing OH adducts of DNA by hydroxycinnamic acid derivatives. A pulse radiolytic study

    International Nuclear Information System (INIS)

    Using pulse radiolytic techniques, it has been demonstrated that the interactions of oxidizing OH adducts of DNA (ssDNA and dsDNA), polyA and polyG with hydroxycinnamic acid derivatives proceed via an electron transfer process (k=5-30x108 dm3 mol-1 s-1). In addition, the rates for fast repair of OH adducts of dAMP, polyA and DNA (ssDNA and dsDNA) are slower than the corresponding rates for the rest OH adducts of DNA constituents. The slower rates for repair of oxidizing OH adducts of dAMP may be the rate determining step during the interaction of hydroxycinnamic acid derivatives with OH adducts of DNA containing the varieties of OH adducts of DNA constituents

  8. Supramolecular chiral host-guest nanoarchitecture induced by the selective assembly of barbituric acid derivative enantiomers

    Science.gov (United States)

    Sun, Xiaonan; Silly, Fabien; Maurel, Francois; Dong, Changzhi

    2016-10-01

    Barbituric acid derivatives are prochiral molecules, i.e. they are chiral upon adsorption on surfaces. Scanning tunneling microscopy reveals that barbituric acid derivatives self-assemble into a chiral guest-host supramolecular architecture at the solid-liquid interface on graphite. The host nanoarchitecture has a sophisticated wavy shape pattern and paired guest molecules are nested insides the cavities of the host structure. Each unit cell of the host structure is composed of both enantiomers with a ratio of 1:1. Furthermore, the wavy patterns of the nanoarchitecture are formed from alternative appearance of left- and right-handed chiral building blocks, which makes the network heterochiral. The functional guest-host nanoarchitecture is the result of two-dimensional chiral amplification from single enantiomers to organizational heterochiral supramolecular self-assembly.

  9. Design and Synthesis of p/m-[p-(un)Substituted Phenylsulfonamido]phenyl β-Diketo Acids and Quinoxalone Derivatives

    Institute of Scientific and Technical Information of China (English)

    ZENG,Cheng-Chu; LI,Xue-Mei; YAN,Hong; ZHONG,Ru-Gang

    2007-01-01

    Diketo acid derivatives are potent and selective HIV-1 integrase inhibitors. To investigate the detailed synthesis of those derivatives, a series of p/m-[p-(un)substituted phenylsulfonamido]phenyl β-diketo acid derivatives have been designed and synthesized. The quinoxalone derivatives as the potential bioisosteres of the biologically labile β-diketoacid pharmacophores have also been synthesized from reactions of the corresponding diketo acids with o-phenylenediamine. The structures of all diketo acid (ester) and quinoxalone derivatives were confirmed by 1H NMR, 13C NMR, IR, HRMS and/or MS (ESI). X-ray crystallographic analysis of 11b demonstrates a similar arrangement of the side chain of quinoxalone derivatives with the parent diketoacids due to the intramolecular hydrogen bond (O…H-N) and the sp2 hybridization configuration of the two nitrogen atoms of the quinoxalone ring.

  10. Environmental effects on the structure of metal ion-DOTA complexes: An ab initio study of radiopharmaceutical metals.

    Energy Technology Data Exchange (ETDEWEB)

    Lau, E Y; Lightstone, F C; Colvin, M E

    2006-02-10

    Quantum mechanical calculations were performed to study the differences between the important radiopharmaceutical metals yttrium (Y) and indium (In) bound by DOTA and modified DOTA molecules. Energies were calculated at the MP2/6-31+G(d)//HF/6-31G(d) levels, using effective core potentials on the Y and In ions. Although the minimum energy structures obtained are similar for both metal ion-DOTA complexes, changes in coordination and local environment significantly affect the geometries and energies of these complexes. Coordination by a single water molecule causes a change in the coordination number and a change in the position of the metal ion in In-DOTA; but, Y-DOTA is hardly affected by water coordination. When one of the DOTA carboxylates is replaced by an amide, the coordination energy for the amide arm shows a large variation between the Y and In ions. Optimizations including water and guandinium moieties to approximate the effects of antibody binding indicate a large energy cost for the DOTA-chelated In to adopt the ideal conformation for antibody binding.

  11. Environmental effects on the structure of metal ion-DOTA complexes: An ab initio study of radiopharmaceutical metals

    International Nuclear Information System (INIS)

    Quantum mechanical calculations were performed to study the differences between the important radiopharmaceutical metals yttrium (Y) and indium (In) bound by DOTA and modified DOTA molecules. Energies were calculated at the MP2/6-31+G(d)//HF/6-31G(d) levels, using effective core potentials on the Y and In ions. Although the minimum energy structures obtained are similar for both metal ion-DOTA complexes, changes in coordination and local environment significantly affect the geometries and energies of these complexes. Coordination by a single water molecule causes a change in the coordination number and a change in the position of the metal ion in In-DOTA; but, Y-DOTA is hardly affected by water coordination. When one of the DOTA carboxylates is replaced by an amide, the coordination energy for the amide arm shows a large variation between the Y and In ions. Optimizations including water and guandinium moieties to approximate the effects of antibody binding indicate a large energy cost for the DOTA-chelated In to adopt the ideal conformation for antibody binding

  12. Structural Investigation for Optimization of Anthranilic Acid Derivatives as Partial FXR Agonists by in Silico Approaches

    OpenAIRE

    Meimei Chen; Xuemei Yang; Xinmei Lai; Jie Kang; Huijuan Gan; Yuxing Gao

    2016-01-01

    In this paper, a three level in silico approach was applied to investigate some important structural and physicochemical aspects of a series of anthranilic acid derivatives (AAD) newly identified as potent partial farnesoid X receptor (FXR) agonists. Initially, both two and three-dimensional quantitative structure activity relationship (2D- and 3D-QSAR) studies were performed based on such AAD by a stepwise technology combined with multiple linear regression and comparative molecular field an...

  13. Heterogeneous and homogeneous catalysis for the hydrogenation of carboxylic acid derivatives: history, advances and future directions.

    Science.gov (United States)

    Pritchard, James; Filonenko, Georgy A; van Putten, Robbert; Hensen, Emiel J M; Pidko, Evgeny A

    2015-06-01

    The catalytic reduction of carboxylic acid derivatives has witnessed a rapid development in recent years. These reactions, involving molecular hydrogen as the reducing agent, can be promoted by heterogeneous and homogeneous catalysts. The milestone achievements and recent results by both approaches are discussed in this Review. In particular, we focus on the mechanistic aspects of the catalytic hydrogenation and highlight the bifunctional nature of the mechanism that is preferred for supported metal catalysts as well as homogeneous transition metal complexes.

  14. Coral cavity sponges depend on reef-derived food resources: stable isotope and fatty acid constraints

    OpenAIRE

    van Duyl, F.C.; Moodley, L; Nieuwland, G.; IJzerloo, L. van; van Soest, R.W.M.; Houtekamer, M.; Meesters, E.H.; Middelburg, J. J.

    2011-01-01

    The diet of cavity sponges on the narrow fringing reefs of Cura double dagger ao, Caribbean was studied. The origin and resources of the bulk food of these sponges, i.e., dissolved organic matter (DOM), were identified using stable carbon and nitrogen isotopes and fatty acid biomarkers. We found that phytoplankton and its derived DOM from the adjacent open sea and from reef overlying water is not the main source of food for most of the sponges examined nor is bacterioplankton. Interestingly, ...

  15. Synthesis and Application of Phenyl Nitrone Derivatives as Acidic and Microbial Corrosion Inhibitors

    OpenAIRE

    Shijun Chen; Kang Zhao; Gang Chen

    2015-01-01

    Nitrone has drawn great attention due to its wide applications as a 1,3-dipole in heterocyclic compounds synthesis and the bioactivities. With the special structure, nitrone can also be used as ligand in inorganic chemistry. Based on the current research, the nitrones are anticipated to be effective inhibitors against acidic and microbial corrosion. The aim of this work is to investigate the inhibitory action of nitrones. In this work, a series of phenyl nitrone derivatives (PN) was synthesiz...

  16. Enzymatic Synthesis of Dipeptide Derivatives Containing Noncoded Amino Acids in Organic Solvents

    Institute of Scientific and Technical Information of China (English)

    YANG,Hong(杨洪); ZHOU,Chuang(周闯); TIAN,Gui-Ling(田桂玲); YE,Yun-Hua(叶蕴华)

    2002-01-01

    A series of dipeptide derivatives containing non-coded amino acis, N-Boc-4-X-Phe-Ala-NHNHNHPh (X= Cl, Br, I, NO2),were synthesized by using thermoase in organic solvents. The physical data were consistent with the same samples prepared by 3-( diethoxyphosphoryloxy)-1, 2, 3-benzotriazin-4 (3H)-one (DEPBT). Influence of different substituted groups of the non-coded amino acids and different organic solvents on the enzymatic peptide synthesis was studied.

  17. Aggregation behavior of cholic acid derivatives in organic solvents and in water

    OpenAIRE

    Willemen, H.M.

    2002-01-01

    In this thesis various cholic acid derivatives are reported that display aggregation in water or in organic solvents. Spontaneous aggregation of single molecules into larger, ordered structures occurs at the borderline of solubility. Amphiphilic compounds, or surfactants, which possess a hydrophobic as well as a hydrophilic part, have a high tendency to form aggregates to minimize unfavorable polar-apolar interactions with the surrounding solvent. There are different types of aggregates in wa...

  18. RNA:DNA Ratio and Other Nucleic Acid Derived Indices in Marine Ecology

    OpenAIRE

    Luis Chícharo; Maria Alexandra Chícharo

    2008-01-01

    Some of most used indicators in marine ecology are nucleic acid-derived indices. They can be divided by target levels in three groups: 1) at the organism level as ecophysiologic indicators, indicators such as RNA:DNA ratios, DNA:dry weight and RNA:protein, 2) at the population level, indicators such as growth rate, starvation incidence or fisheries impact indicators, and 3) at the community level, indicators such as trophic interactions, exergy indices and prey identification. The nu...

  19. Synthesis and in vitro biological evaluation of farnesylthiosalicylic acid derivatives as anti-tumor carcinoma agents

    Institute of Scientific and Technical Information of China (English)

    Yong Ling; You An Xiao; Guang Tong Chen; Dong Geng Wang; Yu Qin Li; Xin Yang Wang; Heng Zheng

    2012-01-01

    Novel farnesylthiosalicylic acid (FTA) derivatives 5a-m with different substituted 1,3,4-thiadiazoles were synthesized.Compounds 5b,5c,5e and 5f displayed anti-tumor activities superior to FTA in most cancer cells tested.Furthermore,5e induced tumor cell apoptosis,which was accompanied by lower Bcl-2 expression,but with higher Bax and caspase 3 expression activities in cancer cells.

  20. Severe Acute Local Reactions to a Hyaluronic Acid-derived Dermal Filler

    OpenAIRE

    Dyke, Susan Van; Hays, Geoffrey P.; Caglia, Anthony E.; Caglia, Michael

    2010-01-01

    Injectable fillers are normally well tolerated by patients with little or no adverse effects. The most common side effects include swelling, redness, bruising, and pain at the injection site. This report describes three cases in which patients injected with a hyaluronic acid-derived injectable filler that is premixed with lidocaine developed adverse reactions including persistent swelling, pain, and nodule formation. Two of the three patients' abscesses were cultured for aerobic and anaerobic...

  1. Local Solvent Acidities in β-Cyclodextrin Complexes with PRODAN Derivatives

    OpenAIRE

    Naughton, Hannah R.; Christopher J. Abelt

    2013-01-01

    The local solvent acidities (SA scale) of six 6-carbonyl-2-aminonaphthalene derivatives as β-cyclodextrin complexes in water are determined through fluorescence quenching. The local polarities (ETN scale) are determined through the shift of the emission center-of-mass. The apparent SA values reflect the solvent structure surrounding the guest’s carbonyl group, whereas the apparent ETN values reveal the net polarity of the entire guest molecule. Comparison of these values affords greater insig...

  2. INFLUENCE OF AROMATIC AMINO ACID DERIVATIVES ON THE LEVELS OF IMMUNE COMPLEXES UNDER IONIZED RADIATION

    OpenAIRE

    A. S. Boyajyan; S. A. Bajinyan; M. H. Malakyan; L. A. Manukyan; E. A. Arakelova; D. E. Yeghiazaryan

    2009-01-01

    Abstract. In the present study, blood levels of circulating immune complexes and of their pathogenic subpopulations were determined in rats following ionizing irradiation. Experimental animals were treated with synthetic Schiff base aromatic amino acid derivatives, nicotinyl-L-tyrosinate or nicotinyl-L-tryptophanate, before irradiation, whereas untreated irradiated rats served as controls. The results obtained demonstrate significantly increased levels of immune complexes, as well as presence...

  3. Simultaneous derivative and multi-component spectrophotometric determination of drotaverine hydrochloride and mefenamic acid in tablets

    Directory of Open Access Journals (Sweden)

    Dahivelkar P

    2007-01-01

    Full Text Available Two new, simple, accurate and economical spectrophotometric methods have been developed for simultaneous estimation of drotaverine hydrochloride and mefenamic acid in two-component tablet formulation. The methods employed are, first derivative spectrophotometry, using zero crossing technique and multicomponent analysis. Both the drugs obey the Beer′s law in the concentration range employed for these methods. The results of analysis are validated by statistical evaluation and recovery studies.

  4. Separation of Six Pyridoncarboylxic Acid Derivatives by Micellar and Microemulsion Electrokinetic Chromatography

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Micellar and microemulsion electrokinetic chromatography (MEKC & MEEKC) separation of six closely structural pyridoncarboylxic acid derivatives were studied and compared. Both anionic surfactant sodium dodecyl sulfate (SDS) and cationic surfactant hexadecyl-trimethyl ammonium bromide (CTAB) were used to form micellar and microemulsion as pseudostation phases, respectively. The effects of the separation conditions on retention time and selectivity were studied. Good resolutions were obtained in selected systems, indicating that there is markably different selectivity between SDS and CTAB systems.

  5. Electrochemical Biosensors Based on Ferroceneboronic Acid and Its Derivatives: A Review

    Directory of Open Access Journals (Sweden)

    Baozhen Wang

    2014-07-01

    Full Text Available We review recent progress in the development of electrochemical biosensors based on ferroceneboronic acid (FcBA and ferrocene (Fc-modified boronic acids. These compounds can be used to construct electrochemical biosensors because they consist of a binding site (i.e., a boronic acid moiety and an electrochemically active part (i.e., an Fc residue. By taking advantage of the unique properties of FcBA and its derivatives, electrochemical sensors sensitive to sugars, glycated hemoglobin (HbA1c, fluoride (F− ions, and so forth have been widely studied. FcBA-based sugar sensors rely on the selective binding of FcBA to 1,2- or 1,3-diol residues of sugars through the formation of cyclic boronate ester bonds. The redox properties of FcBA-sugar adduct differ from those of free FcBA, which forms the basis of the electrochemical determination of sugars. Thus, non-enzymatic glucose sensors are now being actively studied using FcBA and Fc-modified boronic acids as redox markers. Using a similar principle, HbA1c can be detected by FcBA-based electrochemical systems because it contains hydrocarbon chains on the polypeptide chain. HbA1c sensors are useful for monitoring blood glucose levels over the preceding 8–12 weeks. In addition, FcBA and Fc-modified boronic acids have been used for the detection of F− ions due to the selective binding of boronic acid to F− ions. F−-ion sensors may be useful alternatives to conventional ion-selective electrodes sensitive to F− ion. Furthermore, FcBA derivatives have been studied to construct lectin; steroids; nucleotides; salicylic acid; and bacteria sensors. One of the limitations of FcBA-based sensors comes from the fact that FcBA derivatives are added in sample solutions as reagents. FcBA derivatives should be immobilized on the surface of electrodes for developing reagentless sensors.

  6. All-trans retinoic acid promotes smooth muscle cell differentiation of rabbit bone marrow-derived mesenchymal stem cells*

    OpenAIRE

    Su, Zhong-yuan; Ying LI; Zhao, Xiao-Li; Zhang, Ming

    2010-01-01

    Bone marrow-derived mesenchymal stem cells are multipotent stem cells, an attractive resource for regenerative medicine. Accumulating evidence suggests that all-trans retinoic acid plays a key role in the development and differentiation of smooth muscle cells. In the present study, we demonstrate, for the first time, that rabbit bone marrow-derived mesenchymal stem cells differentiate into smooth muscle cells upon the treatment with all-trans retinoic acid. All-trans retinoic acid increased t...

  7. Protective effects of catecholomic acid derivatives on radiation-induced damage of rat liver mitochondria

    International Nuclear Information System (INIS)

    Objective: To evaluate the effects of catecholomic acid derivatives 9501, 9502 and 7601 (CBMIDA) against radiation-induced injury of rat liver mitochondria in vitro. Methods: The injury of rat liver mitochondria was induced by γ-irradiation in vitro. The contents of MDA were assayed by spectrophotometry of TBA. The absorption value at 520 nm was measured to detect swelling of mitochondria. The electron microscopic samples of mitochondria were prepared. Results: All 9501 (5 x 10-6 mol/L), 9502(10-5 mol/L), and 7601 (10-5 mol/L) significantly inhibited radiation-induced increase of MDA information.The swelling of mitochondria induced by irradiation was also prevented by 9501, 7601. The electron micrographs also showed that 9501 markedly reduced the pathological damage of mitochondria induced by γ-irradiation. The mechanisms of anti-oxidative action of catecholomic acid derivatives was discussed. Conclusion: Injurious effect of radiation on rat liver mitochondria can be prevented by catecholomic acid derivatives 9501, 9502 and 7601 (CBMIDA)

  8. [Possible ways of regulating detoxifying processes in the alcohol dehydrogenase reaction with pantothenic acid derivatives].

    Science.gov (United States)

    Chernikevich, I P; Dorofeev, B F; Moĭseenok, A G

    1993-01-01

    Oxidation of derivatives and precursors of pantothenic acid was studied in alcohol dehydrogenase reactions. Despite the presence of free hydroxymethyl groups in a number of pantothenic acid derivatives only panthenol with Km = 8 x 10(-3) M was shown to serve as a substrate for alcohol dehydrogenase from horse liver tissue (EC 1.1.1.1) Pantethine, sodium phosphopantothenate, CoA and acetyl-CoA decreased the rate of ethanol oxidation, where pantethine and sodium phosphopantothenate were competitive inhibitors, while CoA and acetyl-CoA inhibited the enzyme noncompetitively Ki = 1.2 x 10(-2) M, 2.1 x 10(-2) M, 4.4 x 10(-4) M and 5.1 x 10(-4) M, respectively. Metabolic precursors, which were different from pantothenic acid in their structure, were not involved in the alcohol dehydrogenase reaction. Possible regulation of alcohol intoxication using derivatives and precursors of vitamin B3 is discussed. PMID:8511887

  9. Optimising conditions for radiolabelling of DOTA-peptides with 90Y, 111In and 177Lu at high specific activities

    International Nuclear Information System (INIS)

    DOTA-conjugated peptides, such as [DOTA0,Tyr3]octreotide (DOTATOC) and [DOTA0,Tyr3]octreotate (DOTA-tate), can be labelled with radionuclides such as 90Y, 111In and 177Lu. These radiolabelled somatostatin analogues are used for peptide receptor radionuclide therapy (PRRT). Radioligands for PRRT require high specific activities. However, although these radionuclides are produced without addition of carrier, contaminants are introduced during production and as decay products. In this study, parameters influencing the kinetics of labelling of DOTA-peptides were investigated and conditions were optimised to obtain the highest achievable specific activity. The effects of contaminants were systematically investigated, concentration dependently, in a test model mimicking conditions for labelling with minimal molar excess of DOTA-peptides over radionuclide. Kinetics of labelling of DOTA-peptides were optimal at pH 4-4.5; pH 90Y and 177Lu was completed after 20 min at 80 C, while labelling with 111In was completed after 30 min at 100 C. The effects of contaminants were systematically categorised, e.g. Cd2+ is the target and decay product of 111In, and it was found to be a strong competitor with 111In for incorporation in DOTA. In contrast, Zr4+ and Hf4+, decay products of 90Y and 177Lu, respectively, did not interfere with the incorporation of these radionuclides. The following conclusions are drawn: (a) DOTA-peptides can be radiolabelled at high specific activity; (b) reaction kinetics differ for each radionuclide; and (c) reactions can be hampered by contaminants, such as target material and decay products. (orig.)

  10. Overview of Development and Formulation of ¹⁷⁷Lu-DOTA-TATE for PRRT.

    Science.gov (United States)

    Breeman, Wouter A P; Chan, Ho Sze; de Zanger, Rory M S; Konijnenberg, Mark K; de Blois, Erik

    2016-01-01

    Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogs has become an established procedure for the treatment of patients suffering from inoperable neuroendocrine cancers over-expressing somatostatin receptors. Success of PRRT depends on the availability of the radiolabeled peptide with adequately high specific activity, so that required therapeutic efficacy can be achieved without saturating the limited number of receptors available on the target lesions. Specific activity of the radionuclide and the radiolabeled somatostatin analog are therefore an important parameters. Although these analogs have been investigated and improved, and successfully applied for PRRT for more than 15 years, there are still many possibilities for further improvements that fully exploit PRRT with 177Lu-DOTA-TATE. The here summarized data presented herein on increased knowledge of the components of 177Lu-DOTA-TATE (especially the purity of 177Lu and specific activity of 177Lu) and the reaction kinetics during labeling 177Lu-DOTA-TATE clearly show that the peptide dose and dose in GBq can be varied. Here we present an overview of the development, formulation and optimisation of 177Lu-DOTA-TATE, mainly addressing radiochemical parameters.

  11. Comparative evaluation of ior-P1394 and DOTA-TATE for radionuclide therapy

    International Nuclear Information System (INIS)

    Full text: In this study we evaluated the peptides ior-P1394 and DOTA-TATE as radiotherapeutical agents. The first agents were synthesised and obtained by our group and the other one was supplied by the IAEA. Although ior-P1394 and DOTA-TATE were labelled with 188Re and 90Y respectively, with relative high labelling efficiency, both agents under study were evaluated with 125I, and 131I for their biological activity. The radioiodination by Chroramine T method attained yields > 90%. Characterisation via FPLC and chromatographic methods as well as receptor binding and rat biodistribution of the resulting radiolabelled products are described. In vitro stability studies indicated that in saline the biomolecules were stable, while in human serum underwent dissociation at 24h post labelling. In vitro experiments using mice brain cortex membranes showed a dissociation constant (Kd) for ior-P1394 of 11.7 pM, indicating that the obtained species binds with high affinity to somatostatin receptors. Nevertheless, DOTA-TATE labelled with I-125 achieved a Kd of 30.2 nM. Biodistribution studies with 125I-DOTA-TATE in healthy rats exhibited relative high uptake and retention in somatostatin receptor-positive tissues under physiological conditions. Resulting the evaluation more favourable of the radioconjugates under study that of ior-P1394, which exhibited excellent binding properties by its receptor. The results demonstrated that the ior-P1394 might have potential application for diagnosis and therapeutic use. (author)

  12. A DOTA-peptide conjugate by copper-free click chemistry

    OpenAIRE

    Martin, Molly E.; Parameswarappa, Sharavathi G.; O’Dorisio, M. Sue; Pigge, F. Christopher; Schultz, Michael K.

    2010-01-01

    Attachment of DOTA to a novel monofluoro-cyclooctyne facilitates bioconjugation to an azide-modified peptide via Cu-free click chemistry. The resulting conjugate was radiolabeled with 111In to afford a potential targeted molecular imaging agent with high specific activity and in excellent radiochemical purity.

  13. Size-stable solid lipid nanoparticles loaded with Gd-DOTA for magnetic resonance imaging

    International Nuclear Information System (INIS)

    Solid lipid nanoparticles (SLNs) have recently emerged as nontoxic, versatile alternatives to traditional carriers (liposomes, polymeric nanoparticles) for drug delivery. Because SLNs are composed of a solid lipid core, they offer significant protection against chemical degradation of their drug cargo and offer the potential for controlled release. SLNs also hold promise for use as targeted agents and multimodal imaging agents. Here we report the synthesis and characterization of SLNs loaded with gadolinium (1,4,7,10-tetraaza-cyclododecane)-1,4,7,10-tetraacetate (Gd-DOTA) in order to produce a new category of stable T1-weighted (T1w) magnetic resonance imaging (MRI) contrast agents. Systematically varying components in the SLN synthesis, we demonstrated an increase in Gd-DOTA incorporation and an increase in longitudinal relaxivity (r1) through optimizing the amount of surfactant (Span 80) in the 'oil' phase. These highly monodisperse SLNs confirm stable loading of Gd-DOTA and a stable size distribution (∼150 nm) over time in aqueous solution. Relaxivity measurements (1.4 T, 37 C) demonstrate that the r1 of Gd-DOTA does not strongly decrease following encapsulation in SLNs, demonstrating an advantage over liposomes. These Gd-loaded SLNs demonstrate enhanced contrast in vivo at 7 T using T1w MRI and in the future can be loaded with other cargo (hydrophilic or hydrophobic) to enable functionality with other imaging modalities such as optical or positron emission tomography. (authors)

  14. Quantitative structure-activity relationships of antimicrobial fatty acids and derivatives against Staphylococcus aureus

    Institute of Scientific and Technical Information of China (English)

    Hui ZHANG; Lu ZHANG; Li-juan PENG; Xiao-wu DONG; Di WU; Vivian Chi-Hua WU; Feng-qin FENG

    2012-01-01

    Fatty acids and derivatives (FADs) are resources for natural antimicrobials.In order to screen for additional potent antimicrobial agents,the antimicrobial activities of FADs against Staphylococcus aureus were examined using a microplate assay.Monoglycerides of fatty acids were the most potent class of fatty acids,among which monotridecanoin possessed the most potent antimicrobial activity.The conventional quantitative structure-activity relationship (QSAR) and comparative molecular field analysis (CoMFA) were performed to establish two statistically reliable models (conventional QSAR:R2=0.942,Q2LOO=0.910; CoMFA:R2=0.979,Q2=0.588,respectively).Improved forecasting can be achieved by the combination of these two models that provide a good insight into the structureactivity relationships of the FADs and that may be useful to design new FADs as antimicrobial agents.

  15. Synthesis and biological evaluation of sophocarpinic acid derivatives as anti-HCV agents

    Directory of Open Access Journals (Sweden)

    Yinghong Li

    2014-08-01

    Full Text Available Chronic hepatitis C virus (HCV infection has become a major public health burden worldwide. Twenty-two sophocarpinic acid or matrine derivatives were synthesized and their anti-HCV activities were evaluated in vitro. The structure-activity analysis revealed that (i sophocarpinic acids with a D-seco 3-ring structure scaffold were more favorable than matrines with a 4-ring scaffold; (ii the introduction of an electron-withdrawing group on the phenyl ring in 12-N-benzenesulfonyl Δβγ sophocarpinic acids was beneficial for the antiviral activity against HCV. Among them, compounds 9h and 9j exhibited the most potent inhibitory activities on HCV replication with selectivity indies of 70.3 and 30.9, respectively. Therefore, both were selected as antiviral candidates for further investigation.

  16. Synthesis and Cytotoxic Activity on Human Cancer Cells of Novel Isoquinolinequinone-Amino Acid Derivatives.

    Science.gov (United States)

    Valderrama, Jaime A; Delgado, Virginia; Sepúlveda, Sandra; Benites, Julio; Theoduloz, Cristina; Buc Calderon, Pedro; Muccioli, Giulio G

    2016-09-08

    A variety of aminoisoquinoline-5,8-quinones bearing α-amino acids moieties were synthesized from 3-methyl-4-methoxycarbonylisoquinoline-5,8-quinone and diverse l- and d-α-amino acid methyl esters. The members of the series were evaluated for their cytotoxic activity against normal and cancer cell lines by using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. From the current investigation, structure-activity relationships demonstrate that the location and structure of the amino acid fragment plays a significant role in the cytotoxic effects. Moderate to high cytotoxic activity was observed and four members, derived from l-alanine, l-leucine, l-phenylalanine, and d-phenylalanine, were selected as promising compounds by their IC50 ranging from 0.5 to 6.25 μM and also by their good selectivity indexes (≥2.24).

  17. Naturally occurring amino acid derivatives with herbicidal, fungicidal or insecticidal activity.

    Science.gov (United States)

    Lamberth, Clemens

    2016-04-01

    Several naturally occurring amino acid derivatives display significant activities against weeds, fungi and insects: some of them have been even commercialized and are applied as crop protection agents. The 53 most important amino acid natural products with such efficacy are presented in this review together with their natural source, mode of action and biological activity. The diversity of the manifold bacterial, fungal and plantal sources of these compounds is impressive as well as their completely different structural scaffolds, ranging from cyclopeptides via unique non-proteinogenic amino acids to peptidyl nucleosides, the broad range of target enzymes from several different biochemical pathways, which they inhibit and also the plethora of different weeds, fungi and insects they are able to control. PMID:26801938

  18. Hybrid Compounds Strategy in the Synthesis of Oleanolic Acid Skeleton-NSAID Derivatives

    Directory of Open Access Journals (Sweden)

    Anna Pawełczyk

    2016-04-01

    Full Text Available The current study focuses on the synthesis of several hybrid individuals combining a natural oleanolic acid skeleton and synthetic nonsteroidal anti-inflammatory drug moieties (NSAIDs. It studied structural modifications of the oleanolic acid structure by use of the direct reactivity of hydroxyl or hydroxyimino groups at position C-3 of the triterpenoid skeleton with the carboxylic function of anti-inflammatory drugs leading to new perspective compounds with high potential pharmacological activities. Novel ester- and iminoester-type derivatives of oleanolic unit with the different NSAIDs, such as ibuprofen, aspirin, naproxen, and ketoprofen, were obtained and characterized. Moreover, preliminary research of compounds obtaining structure stability under acidic conditions was examined and the PASS method of prediction of activity spectra for substances was used to estimate the potential biological activity of these compounds.

  19. High-performance liquid chromatographic determination of linoleic acid peroxide-derived radicals using electrochemical detection.

    Science.gov (United States)

    Iwahashi, H

    2000-12-29

    High-performance liquid chromatography-electrochemical detection (HPLC-ED) was applied to detect 13-hydroperoxide octadecadienoic acid (13-HPODE)-derived radicals such as the pentyl radical and octanoic acid radical. The 13-HPODE-derived radicals were successfully detected using HPLC-ED by the combined use of the spin-trapping technique with alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN). The 4-POBN-pentyl radical adduct was detected at the retention time of 18.2 +/- 0.3 min on the elution profile of HPLC-ED with an ODS column (15 cm x 4.6 mm I.D.) using a flow-rate of 1.0 ml/min with 50 mM ammonium acetate in 29% (v/v) aqueous acetonitrile. The 4-POBN-octanoic acid radical adduct was also detected at the retention time of 13.7 +/- 0.7 min using a flow-rate of 1.0 ml/min with 50 mM ammonium acetate in 14% (v/v) aqueous acetonitrile. The concentrations of the 4-POBN radical adducts were determined using HPLC-ED without an internal standard. HPLC-ED is 100 times as sensitive as HPLC-electron spin resonance (ESR) under the ESR and ED conditions employed here. Even 1.8 pmol of the 4-POBN-pentyl (or octanoic acid) radical adduct was detectable using PMID:11204234

  20. Optical and thermal properties of azo derivatives of salicylic acid thin films

    Science.gov (United States)

    Ghoneim, M. M.; El-Ghamaz, N. A.; El-Sonbati, A. Z.; Diab, M. A.; El-Bindary, A. A.; Serag, L. S.

    2015-02-01

    N-acryloyl-4-aminosalicylic acid (4-AMSA), monomer (HL) and 5-(4‧-alkyl phenylazo)-N-acryloyl-4-aminosalicylic acid (HLn) are synthesized and characterized with various physico-chemical techniques. Thin films of 5-(4‧-alkyl phenylazo)-N-acryloyl-4-aminosalicylic acid (HLn) are prepared by spin coating technique. The X-ray diffraction (XRD) patterns of 4-aminosalicylic acid (4-ASA) and its derivatives are investigated in powder and thin film forms. Thermal properties of the compounds are investigated by thermogravemetric analysis (TGA). The optical energy gap and the type of optical transition are investigated in the wavelength range (200-2500 nm) for 4-ASA, HL and HLn. The values of fundamental energy gap (Eg) are in the range 3.60-3.69 eV for all compounds and the type of optical transition is found to be indirect allowed. The onset energy gap Eg∗ appeared only for azodye compounds is found to be in the range 0.95-1.55 eV depending on the substituent function groups. The refractive index, n, shows a normal dispersion in the wavelength range 650-2500 nm, while shows anomalous dispersion in the wavelength rang 200-650 nm. The dispersion parameters ε∞, εL, Ed, Eo and N /m∗ are calculated. The photoluminescence phenomena (PL) appear for thin films of 4-ASA and its derivatives show three main emission transitions.

  1. Ring-extended derivatives of gramicidin S with furanoid sugar amino acids in the turn region have enhanced antimicrobial activity

    NARCIS (Netherlands)

    Knijnenburg, A.D.; Spalburg, E.; Neeling, A.J. de; Mars-Groenendijk, R.H.; Noort, D.; Grotenbreg, G.M.; Marel, G.A. van der; Overkleeft, H.S.; Overhand, M.

    2009-01-01

    (Chemical Equation Presented) A series of ring-extended gramicidin S (GS) derivatives containing furanoid sugar amino acids were evaluated. Although the extended GS derivatives have a less well-defined secondary structure as determined by NMR and CD, some derivatives show an improved biological prof

  2. Simultaneous analysis of ellagic acid and coenzyme Q(10) by derivative spectroscopy and HPLC.

    Science.gov (United States)

    Ratnam, D Venkat; Bhardwaj, V; Kumar, M N V Ravi

    2006-09-15

    Antioxidants are gaining tremendous interest as chemopreventive as well as chemotherapeutic agents. Ellagic acid (EA) is a plant derived compound with very poor solubility in water and very low octanol/water partition coefficient and coenzyme Q(10) (CoQ(10)) is a highly lipophilic compound, which is synthesized in the body and can be derived from food supplements as well. The new insights in the combination therapy are promising a better future in many challenging diseases. Synergism is among the key advantages of combination therapy apart from decreased intensity of unwanted effects of a compound, increased patient compliance and reduction in cost of therapy. EA and CoQ(10) supplementation in combination will be beneficial in strengthening the weakened antioxidant defense system in many diseases related to oxidative stress. Here we report first derivative UV spectroscopic and HPLC methods for the simultaneous analysis of these two agents in pharmaceutical preparations. Results obtained indicate that the derivative spectroscopy is as efficient as HPLC method in quantitative analysis. Retention of ellagic acid can be increased using PEG bonded column which is poorly retained on C(18) column. PEG column can be used for rapid simultaneous analysis of EA and CoQ(10), which are having diverse physicochemical properties. PMID:18970780

  3. Quantitative structure activity relationships of some pyridine derivatives as corrosion inhibitors of steel in acidic medium.

    Science.gov (United States)

    El Ashry, El Sayed H; El Nemr, Ahmed; Ragab, Safaa

    2012-03-01

    Quantum chemical calculations using the density functional theory (B3LYP/6-31G DFT) and semi-empirical AM1 methods were performed on ten pyridine derivatives used as corrosion inhibitors for mild steel in acidic medium to determine the relationship between molecular structure and their inhibition efficiencies. Quantum chemical parameters such as total negative charge (TNC) on the molecule, energy of highest occupied molecular orbital (E (HOMO)), energy of lowest unoccupied molecular orbital (E (LUMO)) and dipole moment (μ) as well as linear solvation energy terms, molecular volume (Vi) and dipolar-polarization (π) were correlated to corrosion inhibition efficiency of ten pyridine derivatives. A possible correlation between corrosion inhibition efficiencies and structural properties was searched to reduce the number of compounds to be selected for testing from a library of compounds. It was found that theoretical data support the experimental results. The results were used to predict the corrosion inhibition of 24 related pyridine derivatives.

  4. Characteristic of hyaluronic acid derivative films cross-linked by polyethylene glycol of low water content

    Institute of Scientific and Technical Information of China (English)

    Chen Jinghua; Chen Jingtao; Xu Zheng; Gu Qisheng

    2008-01-01

    Objective: To test the characteristics of byaluronic acid (HA) derivative cross-linked by polyethylene glycol films of low water content. Methods: The cross-linked HA film with 200 μm thickness was got at atmospheric pressure at 25℃ for 5 d. After dried, cross-linked films of 10 mm×10 mm were weighed and immersed in phosphate buffered saline (PBS pH 7.45) at 37℃ for 24 h. Then the solution fraction and water content were estimated. Meanwhile, cross-linked HA derivative films were immersed in phosphate buffered saline (PBS: pH 7.45) at 37℃ for determined time and then implanted subcutaneously in the back of white rats to test in vitro or in vivo degradation characteristic. Results and Conclusion: HA hydrogel cross-linked by polyethylene glycol with water content is as low as 60% and this kind of HA derivative has a slow degradation rate.

  5. Preparation, QC and biological evaluation of 177Lu-DOTA-Tyr3- Octreotate

    International Nuclear Information System (INIS)

    Somatostatin (SS) plays a major role in the physiological regulation of hormones and organs. Radiolabelled somatostatin analogues have been studied for targeted radiotherapy of neuroendocrine tumors and with other malignancies known to bear somatostatin receptor, such as lymphoma, breast cancer, small-cell lung cancer and melanoma. Reactor produced 177Lu is emerging as an important radionuclide for cancer therapy since it decays with half-life of 6.71d by the emission of β- particles with Eβ of 498 keV (78.6), 384 keV (9.1%) and 176 keV (12.2) to stable 177Hf. The 177Lu radionuclide has tissue mean range of 670 μm is considered to be more effective for the treatment of small tumour. High specific activity 177Lu radionuclide (> 8Ci/mg) prepared in our laboratory is considered to be appropriate for labelling peptides. Several experiments for obtaining optimum labelling yield of 177Lu-DOTA-Tyr3-Octreotate under different reaction parameters such pH, incubation time and reaction temperature were performed. Radiochemical purity of 177Lu-DOTA-Tyr3- Octreotate was determined by radio-TLC with C18 plates developed in 70:30 MeOH:10% NH4OAc. Under these conditions 177Lu-DOTA-Tyr3-Octreotate appears at Rf 0.8 while 177Lu-acetate stays at the Rf 0. High labelling yield (>98%) of 177Lu-DOTA-Tyr3-Octreotate was obtained at pH 4.5 at a temperature of 90 deg. C for 30 minutes incubation time. The 177Lu-DOTA-Tyr3-Octreotate was further investigated for stability in acetate/ascorbate buffer and saline at room temperature (12.15 deg. C). The data showed that the labelled complex was stable in buffer and saline medium for a period >24 hours. Animal study of 177Lu-DOTA-Tyr3-Octreotate was performed in ∼200 g male Sprague Dawley rats. Two hundred microlitres of the labelled (80 μCi) were injected into the tail veins of rats and each rat was killed at 1 hour, 2 hours, 6 hours, 12 hours, 24 hours and 72 hours. Countings were performed using Capintec dose calibrator. The

  6. Electrochemical and optical sugar sensors based on phenylboronic acid and its derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Egawa, Yuya; Seki, Toshinobu [Faculty of Pharmaceutical Sciences, Josai University, Keyakidai, Sakado, Saitama 350-0295 (Japan); Takahashi, Shigehiro [Graduate School of Pharmaceutical Sciecnes, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578 (Japan); Anzai, Jun-ichi, E-mail: junanzai@mail.pharm.tohoku.ac.jp [Graduate School of Pharmaceutical Sciecnes, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578 (Japan)

    2011-10-10

    Recent progress in electrochemical and optical sugar sensors based on phenylboronic acid (PBA) and its derivatives as recognition components is reviewed. PBAs are known to bind diol compounds including sugars to form cyclic boronate esters that are negatively charged as a result of the addition of OH{sup -} ions from solution. Based on the formation of PBA charged species, sugars and their derivatives can be detected by means of electrochemical and optical techniques. For the development of PBA-based electrochemical sensing systems or sensors, PBA is modified with a redox-active marker, because PBA itself is electrochemically inactive, and ferrocene derivatives are often employed for this purpose. Ferrocene-modified PBAs have been used as redox-active additives in solution for the electrochemical detection of sugars and derivatives. PBA-modified electrodes have also been constructed as reagentless electrochemical sensors, where PBAs are immobilized on the surface of metal and carbon electrodes through mainly two routes: as a self-assembled monolayer film and as a polymer thin film. PBA-modified electrodes can be successfully used to detect sugars and derivatives through potentiometric and voltammetric responses. In addition, PBA-modified electrodes can be used for the immobilization of glycoenzymes on an electrode surface by the formation of boronate esters with carbohydrate chains in the glycoenzymes, thus resulting in enzyme biosensors. For the development of PBA-based optical sensors, a variety of chromophores and fluorophores have been coupled with PBA. Azobenzene dyes have been most frequently used for the preparation of colorimetric sugar sensors, in which the absorption wavelength and intensity of the dye are dependent on the type and concentration of added sugars. The sensitivity of the sensors is significantly improved based on multi-component systems in which alizalin red S, pyrocatechol violet, starch-iodine complex, and cyclodextrin are employed as

  7. Electrochemical and optical sugar sensors based on phenylboronic acid and its derivatives

    International Nuclear Information System (INIS)

    Recent progress in electrochemical and optical sugar sensors based on phenylboronic acid (PBA) and its derivatives as recognition components is reviewed. PBAs are known to bind diol compounds including sugars to form cyclic boronate esters that are negatively charged as a result of the addition of OH- ions from solution. Based on the formation of PBA charged species, sugars and their derivatives can be detected by means of electrochemical and optical techniques. For the development of PBA-based electrochemical sensing systems or sensors, PBA is modified with a redox-active marker, because PBA itself is electrochemically inactive, and ferrocene derivatives are often employed for this purpose. Ferrocene-modified PBAs have been used as redox-active additives in solution for the electrochemical detection of sugars and derivatives. PBA-modified electrodes have also been constructed as reagentless electrochemical sensors, where PBAs are immobilized on the surface of metal and carbon electrodes through mainly two routes: as a self-assembled monolayer film and as a polymer thin film. PBA-modified electrodes can be successfully used to detect sugars and derivatives through potentiometric and voltammetric responses. In addition, PBA-modified electrodes can be used for the immobilization of glycoenzymes on an electrode surface by the formation of boronate esters with carbohydrate chains in the glycoenzymes, thus resulting in enzyme biosensors. For the development of PBA-based optical sensors, a variety of chromophores and fluorophores have been coupled with PBA. Azobenzene dyes have been most frequently used for the preparation of colorimetric sugar sensors, in which the absorption wavelength and intensity of the dye are dependent on the type and concentration of added sugars. The sensitivity of the sensors is significantly improved based on multi-component systems in which alizalin red S, pyrocatechol violet, starch-iodine complex, and cyclodextrin are employed as indicators

  8. Selective Michael-type addition of a D-glucuronic acid derivative in the synthesis of model substances for uronic acid containing polysaccharides

    Directory of Open Access Journals (Sweden)

    2008-08-01

    Full Text Available A flexible protocol for the preparation of model substances for uronic acid containing polysaccharides is presented. We have synthesized a D-glucuronic acid derivative which is designed so that it easily can be conjugated with different structures and architectures by selective Michael-type addition. By successful coupling of the glucuronic acid derivative to polyethylene glycol with high degree of conversion, products were obtained that were easily characterized and which resembled polysaccharides in terms of solubility and purification methods that could be employed. The model substance can potentially be used to facilitate optimization of low-degree modification reactions of high molecular weight D-glucuronic acid containing polysaccharides.

  9. A Bis-Manganese(II)-DOTA Complex for Pulsed Dipolar Spectroscopy.

    Science.gov (United States)

    Demay-Drouhard, Paul; Ching, H Y Vincent; Akhmetzyanov, Dmitry; Guillot, Régis; Tabares, Leandro C; Bertrand, Hélène C; Policar, Clotilde

    2016-07-01

    High-spin gadolinium(III) and manganese(II) complexes have emerged as alternatives to standard nitroxide radical spin labels for measuring nanometric distances by using pulsed electron-electron double resonance (PELDOR or DEER) at high fields/frequencies. For certain complexes, particularly those with relatively small zero-field splitting (ZFS) and short distances between the two metal centers, the pseudosecular term of the dipolar coupling Hamiltonian is non-negligible. However, in general, the contribution from this term during conventional data analysis is masked by the flexibility of the molecule of interest and/or the long tethers connecting them to the spin labels. The efficient synthesis of a model system consisting of two [Mn(dota)](2-) (MnDOTA; DOTA(4-) =1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate) directly connected to the ends of a central rodlike oligo(phenylene-ethynylene) (OPE) spacer is reported. The rigidity of the OPE is confirmed by Q-band PELDOR measurements on a bis-nitroxide analogue. The Mn(II) -Mn(II) distance distribution profile determined by W-band PELDOR is in reasonable agreement with one simulated by using a simple rotamer analysis. The small degree of flexibility arising from the linking MnDOTA arm appears to outweigh the contribution from the pseudosecular term at this interspin distance. This study illustrates the potential of MnDOTA-based spin labels for measuring fairly short nanometer distances, and also presents an interesting candidate for in-depth studies of pulsed dipolar spectroscopy methods on Mn(II) -Mn(II) systems. PMID:27017296

  10. Production of chlorogenic acid and its derivatives in hairy root cultures of Stevia rebaudiana.

    Science.gov (United States)

    Fu, Xiao; Yin, Zhong-Ping; Chen, Ji-Guang; Shangguan, Xin-Chen; Wang, Xiaoqiang; Zhang, Qing-Feng; Peng, Da-Yong

    2015-01-14

    Chlorogenic acid and its derivatives (CADs) are valuable bioactive plant secondary metabolites with many health benefits. In the present study, Stevia rebaudiana hairy root cultures were established, and the culture conditions for the production of CADs were optimized. The hairy roots were induced by coculture of S. rebaudiana leaves and Agrobacterium rhizogenes (C58C1) after infection, which were further verified by PCR detection of rolB and rolC genes. HPLC-MS and HPLC analysis showed that chlorogenic acid (3-caffeoylquinic acid, 3-CQA), 3,5-dicaffeoylquinic acid (3,5-CQA), and 4,5-dicaffeoylquinic acid (4,5-CQA) were the major CADs in the hairy roots. Eight single roots with rapid growth rate were selected. Among them, T3 had the highest yield of CADs. B5 medium supplemented with 40 g/L sucrose was more suitable for the production of CADs than others. Under optimal culture conditions, the total content of these three compounds reached 105.58 mg/g and total yield was 234.40 mg/100 mL. PMID:25548875

  11. Production of chlorogenic acid and its derivatives in hairy root cultures of Stevia rebaudiana.

    Science.gov (United States)

    Fu, Xiao; Yin, Zhong-Ping; Chen, Ji-Guang; Shangguan, Xin-Chen; Wang, Xiaoqiang; Zhang, Qing-Feng; Peng, Da-Yong

    2015-01-14

    Chlorogenic acid and its derivatives (CADs) are valuable bioactive plant secondary metabolites with many health benefits. In the present study, Stevia rebaudiana hairy root cultures were established, and the culture conditions for the production of CADs were optimized. The hairy roots were induced by coculture of S. rebaudiana leaves and Agrobacterium rhizogenes (C58C1) after infection, which were further verified by PCR detection of rolB and rolC genes. HPLC-MS and HPLC analysis showed that chlorogenic acid (3-caffeoylquinic acid, 3-CQA), 3,5-dicaffeoylquinic acid (3,5-CQA), and 4,5-dicaffeoylquinic acid (4,5-CQA) were the major CADs in the hairy roots. Eight single roots with rapid growth rate were selected. Among them, T3 had the highest yield of CADs. B5 medium supplemented with 40 g/L sucrose was more suitable for the production of CADs than others. Under optimal culture conditions, the total content of these three compounds reached 105.58 mg/g and total yield was 234.40 mg/100 mL.

  12. Characteristics of Hyaluronic Acid Derivative Cross-linked by Polyethylene Glycol

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Characteristic and dynamic viscosities of Hyaluronic acid ( HA ) derivative modified by polyethylene glycol (PEG) were tested with different reaction times (6 h,12 h,18 h and 24 h ) , different molar ratio of HA/PEG ( 1/10,1/5,1/3 and 1/2), different molecular weight of PEG(400,6 000 and 20 000) and mass fraction is 0.4% by Wushi Viscosimeter and L- 90 Rheometer at 25 ℃. Characteristic viscosity of HA derivative had the largest value in 12 h, which decreased with increasing of PEG molecular weight, but its aqueous dynamic viscosity increased with increment of PEG molecular weight. Meanwhile, we tested dynamic mechanic properties of HA derivative by 3ARES3 Rheometer at 25 ℃ to study viscoelastic changes and to compare change difference from viscosity to elasticity with the changes of vibration frequency between unmodified HA and HA derivative.Change from low vibrated frequency to high one of solution resulted in change from viscosity to elasticity of solution. In conclusion, as to the rheological properties, structure-modified HA derivative meets the requirement of biomnterial .

  13. Formation and Characterization of Self-Assembled Phenylboronic Acid Derivative Monolayers toward Developing Monosaccaride Sensing-Interface

    Directory of Open Access Journals (Sweden)

    Kwangnak Koh

    2007-08-01

    Full Text Available We designed and synthesized phenylboronic acid as a molecular recognitionmodel system for saccharide detection. The phenylboronic acid derivatives that haveboronic acid moiety are well known to interact with saccharides in aqueous solution; thus,they can be applied to a functional interface of saccharide sensing through the formation ofself-assembled monolayer (SAM. In this study, self-assembled phenylboronic acidderivative monolayers were formed on Au surface and carefully characterized by atomicforce microscopy (AFM, Fourier transform infrared reflection absorption spectroscopy(FTIR-RAS, surface enhanced Raman spectroscopy (SERS, and surface electrochemicalmeasurements. The saccharide sensing application was investigated using surface plasmonresonance (SPR spectroscopy. The phenylboronic acid monolayers showed goodsensitivity of monosaccharide sensing even at the low concentration range (1.0 × 10-12 M.The SPR angle shift derived from interaction between phenylboronic acid andmonosaccharide was increased with increasing the alkyl spacer length of synthesizedphenylboronic acid derivatives.

  14. Catalytic Kinetic Determination of Micro Amounts of Oxalic Acid by Second-Order Derivative Oscillopolarography

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    It was found that micro amounts of oxalate showed a very strong catalytic effect on the slow reaction between K2Cr2O7 and Orange Ⅳ in a diluted sulfuric acid medium in a water bath at 70 ℃. Orange Ⅳ exhibited a sensitive second-order derivative polarographic wave at -0.50 V(vs. SCE). This provides the basis for a sensitive and selective catalytic kinetic method for oxalate determination with second-order derivative oscillopolarography. The effects of sulphuric acid, K2Cr2O7, and orange Ⅳ concentrations, reaction temperature and reaction time were investigated. A calibration curve of oxalate in the range of 0.1—2.0 μg/mL was obtained by the fixed-time procedure. The detection limit was 0.03 μg/ mL. The possible interference from co-existing substances or ions was examined. The new method has a high sensitivity and a good selectivity compared to other existing methods for oxalic acid determination. It has been applied to the determination of micro amounts of oxalate in real urine samples with satisfactory results.

  15. Production of fatty acid-derived oleochemicals and biofuels by synthetic yeast cell factories.

    Science.gov (United States)

    Zhou, Yongjin J; Buijs, Nicolaas A; Zhu, Zhiwei; Qin, Jiufu; Siewers, Verena; Nielsen, Jens

    2016-01-01

    Sustainable production of oleochemicals requires establishment of cell factory platform strains. The yeast Saccharomyces cerevisiae is an attractive cell factory as new strains can be rapidly implemented into existing infrastructures such as bioethanol production plants. Here we show high-level production of free fatty acids (FFAs) in a yeast cell factory, and the production of alkanes and fatty alcohols from its descendants. The engineered strain produces up to 10.4 g l(-1) of FFAs, which is the highest reported titre to date. Furthermore, through screening of specific pathway enzymes, endogenous alcohol dehydrogenases and aldehyde reductases, we reconstruct efficient pathways for conversion of fatty acids to alkanes (0.8 mg l(-1)) and fatty alcohols (1.5 g l(-1)), to our knowledge the highest titres reported in S. cerevisiae. This should facilitate the construction of yeast cell factories for production of fatty acids derived products and even aldehyde-derived chemicals of high value. PMID:27222209

  16. [Antithrombotic therapy after myocardial infarction: arguments for the use of acetylsalicylic acid and coumarin derivatives].

    Science.gov (United States)

    Waskowsky, W M; Brouwer, A; Verheugt, F W A

    2005-01-01

    Patients who survived myocardial infarction and who are being treated with the current optimal therapy (antithrombotics, statins and beta-blockers), have a 10-20% chance of death, re-infarction and stroke within in the first year. A possible explanation for this could be an increased activation and generation ofthrombin for at least 6 months following the cardiovascular event preceding preventative therapy. Acetylsalicylic acid and clopidogrel do not affect activation by thrombin of the platelet aggregation and the clotting cascade. The additional use of cumarin derivatives could therefore reduce the chance of recurring thrombotic events, and subsequently improve prognosis. Since the nineteen-nineties several randomised trials have been conducted to study the clinical relevance ofcumarin derivatives both with and without acetylsalicylic acid, in patients who had had a myocardial infarction. The conclusions of these studies were not unambiguous. If the international normalized ratio (INR) was kept > 2 for a long period, by means of frequent check-ups and effective dosage adjustment, the chance of death, recurrent myocardial infarction or stroke was 30-50% lower than when acetylsalicylic acid only was used. The risk of bleeding was raised by 2-4 times, but there were no life-threatening episodes of bleeding. In view of the recent development of anticoagulant agents, for which monitoring seems to be becoming unnecessary, identification of patients who would benefit most from a combined antithrombotic strategy is warranted. PMID:15688836

  17. Production of fatty acid-derived oleochemicals and biofuels by synthetic yeast cell factories.

    Science.gov (United States)

    Zhou, Yongjin J; Buijs, Nicolaas A; Zhu, Zhiwei; Qin, Jiufu; Siewers, Verena; Nielsen, Jens

    2016-01-01

    Sustainable production of oleochemicals requires establishment of cell factory platform strains. The yeast Saccharomyces cerevisiae is an attractive cell factory as new strains can be rapidly implemented into existing infrastructures such as bioethanol production plants. Here we show high-level production of free fatty acids (FFAs) in a yeast cell factory, and the production of alkanes and fatty alcohols from its descendants. The engineered strain produces up to 10.4 g l(-1) of FFAs, which is the highest reported titre to date. Furthermore, through screening of specific pathway enzymes, endogenous alcohol dehydrogenases and aldehyde reductases, we reconstruct efficient pathways for conversion of fatty acids to alkanes (0.8 mg l(-1)) and fatty alcohols (1.5 g l(-1)), to our knowledge the highest titres reported in S. cerevisiae. This should facilitate the construction of yeast cell factories for production of fatty acids derived products and even aldehyde-derived chemicals of high value.

  18. Nutritional stability of various naturally occurring monoglutamate derivatives of folic acid.

    Science.gov (United States)

    O'Broin, J D; Temperley, I J; Brown, J P; Scott, J M

    1975-05-01

    The nutritional stabilities of four major dietary folates were studied as their corresponding monoglutamates and were compared to pteroylglutamate (folic acid) itself. The study of the monoglutamyl rather than polyglutamyl forms was justified since the former are formed during the course of digestion and also addition of extra glutamyl residues is unlikely to affect the types of nutritional instability associated with these derivatives. Since ability to support growth in Lactobacillus casei is known to reflect nutritional activity in man this organism was used in the stability studies. It was found that pteroylglutamate and 5-formyltetrahydropteroylglutamate had nutritional stabilities of the order of weeks although the stability of the former was decreased by phosphate. Surprisingly 10-formyltetrahydropteroylglutamate was nutritionally more stable than expected, possibly due to its conversion to the more stable oxidized 10-formylpteroylglutamate or to the reduced 5-formyl derivative. In contrast 5-methyltetrahydropteroylglutamate was much less stable nutritionally than expected.Unsubstituted tetrahydropteroylglutamate was most unstable nutritionally but in contrast to the other derivatives examined it was more stable under acidic than basic conditions. Ascorbate was found to be a far superior stabilizing agent than 2-mercaptoethanol at comparable concentrations. PMID:236647

  19. 90Y-DOTA-CHS Microspheres for Live Radiomicrosphere Therapy: Preliminary In Vivo Lung Radiochemical Stability Studies

    Directory of Open Access Journals (Sweden)

    Alejandro Amor-Coarasa

    2014-01-01

    Full Text Available Chitosan (CHS is used to prepare microspheres of 31 ± 8 µm size. Surface modification with p-SCN-Bn-DOTA was performed. A maximum 90Y capacity was found to be 12.1 ± 4.4 µCi/particle. The best obtained labeling yield was 87.7 ± 0.6%. More than 90% in vitro stability was found. Particle in vitro degradation half-life in PBS was found to be greater than 21 days. In vivo studies with 90Y-DOTA-CHS showed more than 95% of the injected activity (decay corrected in the lungs 24 hours after tail vein administration. 90Y-DOTA-CHS in vivo label stability was superior to resin microspheres. The addition of p-SCN-Bn-DOTA served as a radioprotectant for bone marrow as the 5% 90Y released, during the first 24 hours, was quickly eliminated via urine.

  20. 90Y-DOTA-CHS Microspheres for Live Radio microsphere Therapy: Preliminary In Vivo Lung Radiochemical Stability Studies

    International Nuclear Information System (INIS)

    Chitosan (CHS) is used to prepare microspheres of 31 ± 8 µm size. Surface modification with p-SCN-Bn-DOTA was performed. A maximum 90Y capacity was found to be 12.1 ± 4.4 µCi/particle. The best obtained labeling yield was 87.7 ± 0.6%. More than 90% in vitro stability was found. Particle in vitro degradation half-life in PBS was found to be greater than 21 days. In vivo studies with 90Y-DOTA-CHS showed more than 95% of the injected activity (decay corrected) in the lungs 24 hours after tail vein administration. 90Y-DOTA-CHS in vivo label stability was superior to resin microspheres. The addition of p-SCN-Bn-DOTA served as a radioprotectant for bone marrow as the 5% 90Y released, during the first 24 hours, was quickly eliminated via urine.

  1. Experimental and Theoretical Investigations of Spectral, Tautomerism and Acid-Base Properties of Schiff Bases Derived from Some Amino Acids

    Energy Technology Data Exchange (ETDEWEB)

    Ebead, Y. H.; Salman, H. M. A.; Abdellah, M. A. [South Valley University, Qena (Egypt)

    2010-04-15

    The electronic absorption spectra of five Schiff bases derived from 2-hydroxy-1-naphthaldehyde with glycine, alanine, leucine, valine and phenylalanine have been measured in various solvents. The observed bands were assigned to the proper electronic transitions and compared with the predicted transitions at the semiempirical level of theory. The calculated equilibrium constants are in agreement with the experimental results, predicting the existence of all studied compounds predominantly or completely in keto-imine tautomerism. On the other hand, a correlation between ν (cm{sup -1}) (main frequency of each compound) and the well known solvent parameters E{sub T} (30), ε{sub r}, π* has been made. Furthermore, the acid dissociation constants, pK{sub a}, were determined by using three different spectrophotometric methods.

  2. Effects of amino acid derivatives on physical, mental, and physiological activities.

    Science.gov (United States)

    Luckose, Feby; Pandey, Mohan Chandra; Radhakrishna, Kolpe

    2015-01-01

    Nutritional ergogenic aids have been in use for a long time to enhance exercise and sports performance. Dietary components that exhibit ergogenic activity are numerous and their consumption is common and popular among athletes. They often come under scrutiny by legal authorities for their claimed benefits and safety concerns. Amino acid derivatives are propagated as being effective aids to enhance physical and mental performance in many ways, even though studies have pointed out that individuals who are deficient are more likely to benefit from dietary supplementation of amino acid derivatives than normal humans. In this review, some of the most common and widely used amino acids derivatives in sports and athletics namely creatine, tyrosine, carnitine, HMB, and taurine have been discussed for their effects on exercise performance, mental activity as well as body strength and composition. Creatine, carnitine, HMB, and taurine are reported to delay the onset of fatigue, improve exercise performance, and body strength. HMB helps in increasing fat-free mass and reduce exercise induced muscle injury. Taurine has been found to reduce oxidative stress during exercise and also act as an antihypertensive agent. Although, studies have not been able to find any favorable effect of tyrosine administration on exercise performance, it has been proved to be very effective in fighting stress, improving mood and cognitive performance particularly in sleep-deprived subjects. While available data from published studies and findings are equivocal about the efficacy of creatine, tyrosine, and HMB, more comprehensive researches on carnitine and taurine are necessary to provide evidence for the theoretical basis of their ergogenic role in nutritional modification and supplementation. PMID:24279396

  3. Bioactive 1,4-dihydroisonicotinic acid derivatives prevent oxidative damage of liver cells.

    Science.gov (United States)

    Borovic, Suzana; Tirzitis, Gunars; Tirzite, Dace; Cipak, Ana; Khoschsorur, Gholam A; Waeg, Georg; Tatzber, Franz; Scukanec-Spoljar, Mira; Zarkovic, Neven

    2006-05-10

    1,4-Dihydroisonicotinic acid derivatives (1,4-DHINA) are compounds closely related to derivatives of 1,4-dihydropyridine, a well-known calcium channel antagonists. 1,4-DHINA we used were derived from a well-known antioxidant Diludin. Although some compounds have neuromodulatory or antimutagenic properties, their activity mechanisms are not well known. This study was performed to obtain data on antioxidant and bioprotective activities of: 2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydroisonicotinic acid (Ia); sodium 2-(2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine-4-carboxamido)glutamate (Ib) and sodium 2-(2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine-4-carboxamido)ethane-sulphate (Ic). 1,4-DHINA's activities were studied in comparison to Trolox by: N,N-Diphenyl-N'-picrylhydrazyl (DPPH*), deoxyribose degradation, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) radical scavenging and antioxidative capacity assays; copper-induced lipid peroxidation of cultured rat liver cells (malondialdehyde determination by high performance liquid chromatography and 4-hydroxynonenal-protein conjugates by dot-blot); (3)H-thymidine incorporation and trypan blue assay for liver cells growth and viability. In all assays used Ia was the most potent antioxidant. Ia was also a potent antioxidant at non-toxic concentrations for liver cell cultures. It completely abolished, while Ic only slightly decreased copper-induced lipid peroxidation of liver cells. Thus, antioxidant capacities are important activity principle of Ia, which was even superior to Trolox in the cell cultures used, while activity principles of Ic and Ib remain yet to be determined. PMID:16600211

  4. Initial evaluation of {sup 227}Th-p-benzyl-DOTA-rituximab for low-dose rate {alpha}-particle radioimmunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Dahle, Jostein [Department of Radiation Biology, Rikshospitalet-Radiumhospitalet HE, Montebello, 0310 Oslo (Norway)]. E-mail: jostein.dahle@labmed.uio.no; Borrebaek, Jorgen [Algeta ASA, Kjelsasveien 172 A, 0411 Oslo (Norway); Melhus, Katrine B. [Department of Radiation Biology, Rikshospitalet-Radiumhospitalet HE, Montebello, 0310 Oslo (Norway); Bruland, Oyvind S. [Department of Clinical Medicine, University of Oslo, 0316 Oslo (Norway); Department of Oncology, Rikshospitalet-Radiumhospitalet HE, Montebello, 0310 Oslo (Norway); Salberg, Gro [Algeta ASA, Kjelsasveien 172 A, 0411 Oslo (Norway); Olsen, Dag Rune [Department of Radiation Biology, Rikshospitalet-Radiumhospitalet HE, Montebello, 0310 Oslo (Norway); Larsen, Roy H. [Algeta ASA, Kjelsasveien 172 A, 0411 Oslo (Norway)

    2006-02-15

    Radioimmunotherapy has proven clinically effective in patients with non-Hodgkin's lymphoma. Radioimmunotherapy trials have so far been performed with {beta}-emitting isotopes. In contrast to {beta}-emitters, the shorter range and high linear energy transfer (LET) of {alpha} particles allow for more efficient and selective killing of individually targeted tumor cells. However, there are several obstacles to the use of {alpha}-particle immunotherapy, including problems with chelation chemistry and nontarget tissue toxicity. The {alpha}-emitting radioimmunoconjugate {sup 227}Th-DOTA-p-benzyl-rituximab is a new potential anti-lymphoma agent that might overcome some of these difficulties. The present study explores the immunoreactivity, in vivo stability and biodistribution, as well as the effect on in vitro cell growth, of this novel radioimmunoconjugate. To evaluate in vivo stability, uptake in balb/c mice of the {alpha}-particle-emitting nuclide {sup 227}Th alone, the chelated form, {sup 227}Th-p-nitrobenzyl-DOTA and the radioimmunoconjugate {sup 227}Th-DOTA-p-benzyl-rituximab was compared in a range of organs at increasing time points after injection. The immunoreactive fraction of {sup 227}Th-DOTA-p-benzyl-rituximab was 56-65%. During the 28 days after injection of radioimmunoconjugate only, very modest amounts of the {sup 227}Th had detached from DOTA-p-benzyl-rituximab, indicating a relevant stability in vivo. The half-life of {sup 227}Th-DOTA-p-benzyl-rituximab in blood was 7.4 days. Incubation of lymphoma cells with {sup 227}Th-DOTA-p-benzyl-rituximab resulted in a significant antigen-dependent inhibition of cell growth. The data presented here warrant further studies of {sup 227}Th-DOTA-p-benzyl-rituximab.

  5. Lanthanide(III) Complexes of DOTA-Glycoconjugates: A Potential New Class of Lectin-Mediated Medical Imaging Agents

    OpenAIRE

    André, João P.; Geraldes, Carlos F. G. C.; Martins, José A.; Merbach, André E.; Prata, Maria I. M.; Santos, Ana C; Lima, João J. P. de; Tóth, Éva

    2004-01-01

    The synthesis and characterization of a new class of DOTA (1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane) monoamide-linked glycoconjugates (glucose, lactose and galactose) of different valencies (mono, di and tetra) and their Sm(III), Eu(III) and Gd(III) complexes are reported. The proton NMR spectrum of Eu(III)-DOTALac(III) shows the predominance of a single structural isomer of square antiprismatic geometry of the DOTA chelating moiety and fast ...

  6. [177Lu]-DOTA0-Tyr3-octreotate: A Potential Targeted Radiotherapeutic for the Treatment of Medulloblastoma

    OpenAIRE

    Vaidyanathan, Ganesan; Affleck, Donna J.; Zhao, Xiao-Guang; Keir, Stephen T.; Zalutsky, Michael R.

    2010-01-01

    Medulloblastoma, the most common pediatric brain tumor, is difficult to treat because conventional therapeutic approaches result in significant toxicity to normal central nervous system tissues, compromising quality of life. Given the fact that medulloblastomas express the somatostatin subtype 2 receptor, [177Lu-DOTA0,Tyr3]octreotate ([177Lu]DOTA-TATE) could be a potentially useful targeted radiotherapeutic for the treatment of this malignancy. The current study was undertaken to evaluate thi...

  7. Initial evaluation of 227Th-p-benzyl-DOTA-rituximab for low-dose rate α-particle radioimmunotherapy

    International Nuclear Information System (INIS)

    Radioimmunotherapy has proven clinically effective in patients with non-Hodgkin's lymphoma. Radioimmunotherapy trials have so far been performed with β-emitting isotopes. In contrast to β-emitters, the shorter range and high linear energy transfer (LET) of α particles allow for more efficient and selective killing of individually targeted tumor cells. However, there are several obstacles to the use of α-particle immunotherapy, including problems with chelation chemistry and nontarget tissue toxicity. The α-emitting radioimmunoconjugate 227Th-DOTA-p-benzyl-rituximab is a new potential anti-lymphoma agent that might overcome some of these difficulties. The present study explores the immunoreactivity, in vivo stability and biodistribution, as well as the effect on in vitro cell growth, of this novel radioimmunoconjugate. To evaluate in vivo stability, uptake in balb/c mice of the α-particle-emitting nuclide 227Th alone, the chelated form, 227Th-p-nitrobenzyl-DOTA and the radioimmunoconjugate 227Th-DOTA-p-benzyl-rituximab was compared in a range of organs at increasing time points after injection. The immunoreactive fraction of 227Th-DOTA-p-benzyl-rituximab was 56-65%. During the 28 days after injection of radioimmunoconjugate only, very modest amounts of the 227Th had detached from DOTA-p-benzyl-rituximab, indicating a relevant stability in vivo. The half-life of 227Th-DOTA-p-benzyl-rituximab in blood was 7.4 days. Incubation of lymphoma cells with 227Th-DOTA-p-benzyl-rituximab resulted in a significant antigen-dependent inhibition of cell growth. The data presented here warrant further studies of 227Th-DOTA-p-benzyl-rituximab

  8. Synthesis of a DOTA(Gd3+)-conjugate of proton-pump inhibitor pantoprazole for gastric wall imaging studies

    OpenAIRE

    Maharvi, Ghulam M.; Bharucha, Adil E.; Fauq, Abdul H.

    2012-01-01

    Magnetic resonance imaging (MRI) is used to evaluate gastrointestinal (GI) structure and functions in humans. Despite filling the viscus lumen with a contrast agent, visualization of the viscus wall is limited. To overcome this limitation, we de novo synthesized a conjugate that covalently combines a Gd-based MRI contrast agent, encaged with a chelating agent (DOTA), with pantoprazole, which is a widely used proton pump inhibitor that binds to proton pumps in the stomach and colon. The DOTA l...

  9. Hydrogels formed by enantioselective self-assembly of histidine-derived amphiphiles with tartaric acid.

    Science.gov (United States)

    Zhang, Fanjun; Xu, Zhenghu; Dong, Shuli; Feng, Lei; Song, Aixin; Tung, Chen-Ho; Hao, Jingcheng

    2014-07-21

    Two chiral enantiomers of histidine-derived amphiphilic gelators, (4R,6S)-UIPCA and (4S,6R)-UIPCA, were synthesized through Pictet-Spengler reaction and their gelation behaviors with different organic acids were investigated. Interestingly, the chiral enantiomers of UIPCA showed smart enantioselectivity for gelating tartaric acid enantiomers to form hydrogels with excellent mechanical strength. The TEM and SEM images demonstrated that the hydrogels were composed of networks by physical entanglement of nanofibers with high aspect ratios. The formation of nanofibers was considered to be driven by the interplay of hydrogen bonding, electrostatic attraction, and hydrophobic interaction, which was supported by XRD and FT-IR spectra. The hydrogels exhibited sensitive response to a series of external stimuli, such as temperature, metal ions, and host-guest interactions, to realize the reversible gel-sol transition. The property of the gelation was elaborated and the gelators were expected to find their applications in chiral discrimination. PMID:24865976

  10. Synthesis and Structural Characterization of 1- and 2-Substituted Indazoles: Ester and Carboxylic Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Isabel Bento

    2006-11-01

    Full Text Available A series of indazoles substituted at the N-1 and N-2 positions with ester-containing side chains -(CH2nCO2R of different lengths (n = 0-6, 9, 10 are described.Nucleophilic substitution reactions on halo esters (X(CH2nCO2R by 1H-indazole inalkaline solution lead to mixtures of N-1 and N-2 isomers, in which the N-1 isomerpredominates. Basic hydrolysis of the ester derivatives allowed the synthesis of thecorresponding indazole carboxylic acids. All compounds were fully characterised bymultinuclear NMR and IR spectroscopies, MS spectrometry and elemental analysis; theNMR spectroscopic data were used for structural assignment of the N-1 and N-2 isomers.The molecular structure of indazol-2-yl-acetic acid (5b was determined by X-raydiffraction, which shows a supramolecular architecture involving O2-H...N1intermolecular hydrogen bonds.

  11. Molecular interaction of acetylcholinesterase with carnosic acid derivatives: a neuroinformatics study.

    Science.gov (United States)

    Merad, M; Soufi, W; Ghalem, S; Boukli, F; Baig, M H; Ahmad, K; Kamal, Mohammad A

    2014-04-01

    Alzheimer's disease is a progressive degenerative disease of the brain marked by gradual and irreversible declines in cognitive functions. Acetylcholinesterase (AChE) plays a biological role in the termination of nerve impulse transmissions at cholinergic synapses by rapid hydrolysis of its substrate, "acetylcholine". The deficit level of acetylcholine leads to deprived nerve impulse transmission. Thus the cholinesterase inhibitors would reverse the deficit in acetylcholine level and consequently may reverse the memory impairments, which is characteristic of the Alzheimer's disease. The molecular interactions between AChE and Carnosic acid, a well known antioxidant substance found in the leaves of the rosemary plant has always been an area of interest. Here in this study we have performed in silico approach to identify carnosic acid derivatives having the potential of being a possible drug candidate against AChE. The best candidates were selected on the basis of the results of different scoring functions. PMID:24059305

  12. Design, synthesis and antitumor activity of novel D-glucuronic acid derivatives.

    Science.gov (United States)

    el-Nezhawy, Ahmed O H; Adly, Frady G; Eweas, Ahmed F; Hanna, Atef G; el-Kholy, Yehya M; el-Syed, Shahenaz H; el-Naggar, Tarek B A

    2011-11-01

    A series of D-glucuronic acid derivatives were chemically synthesized including acetylated and deacetylated glucuronamides, as well as N-glucuronides starting from the D-glucuronic acid itself by means of protection/deprotection, activation and condensation protocols. Structure elucidation of all products along with optimization of the synthetic steps is described. The synthesized compounds were evaluated for their in vitro antitumor activity against MCF-7, TK-10 and UACC-62 cell lines. The compounds 4, 5, 7, 8, 14, 16 and 18 were the most active against TK-10 cell line. On the other hand, the most active compounds against the MCF-7 cell line were 9, 18 and 20. However, compounds 7-10 13-15 and 17 were the most active against the UACC-62 cell line.

  13. Solution structure of human acidic fibroblast growth factor and interaction with heparin-derived hexasaccharide

    International Nuclear Information System (INIS)

    Fibroblast growth factors (FGFs) bind to extracellular matrices, especially heparin-like carbohydrates of heparansulfate proteoglycans which stabilize FGFs to protect against inactivation by heat, acid, proteolysis and oxidation. Moreover, binding of FGFs to cell surface proteoglycans promotes to form oligomers, which is essential for receptor oligomerization and activation. In the present study, we determined the solution structure of acidic FGF using a series of triple resonance multi-dimensional NMR experiments and simulated annealing calculations. Furthermore, we prepared the sample complexed with a heparin-derived hexasaccharide which is a minimum unit for aFGF binding. From the chemical shift differences between free aFGF and aFGF-heparin complex, we concluded that the major heparin binding site was located on the regions 110-131 and 17-21. The binding sites are quite similar to those observed for bFGF-heparin hexasaccharide complex, showing that both FGFs recognize heparin- oligosaccharides in a similar manner

  14. Diverse Bacterial PKS Sequences Derived From Okadaic Acid-Producing Dinoflagellates

    Directory of Open Access Journals (Sweden)

    Kathleen S. Rein

    2008-05-01

    Full Text Available Okadaic acid (OA and the related dinophysistoxins are isolated from dinoflagellates of the genus Prorocentrum and Dinophysis. Bacteria of the Roseobacter group have been associated with okadaic acid producing dinoflagellates and have been previously implicated in OA production. Analysis of 16S rRNA libraries reveals that Roseobacter are the most abundant bacteria associated with OA producing dinoflagellates of the genus Prorocentrum and are not found in association with non-toxic dinoflagellates. While some polyketide synthase (PKS genes form a highly supported Prorocentrum clade, most appear to be bacterial, but unrelated to Roseobacter or Alpha-Proteobacterial PKSs or those derived from other Alveolates Karenia brevis or Crytosporidium parvum.

  15. Linoleic acid derivative DCP-LA improves learning impairment in SAMP8.

    Science.gov (United States)

    Yaguchi, Takahiro; Nagata, Tetsu; Mukasa, Takeshi; Fujikawa, Hirokazu; Yamamoto, Hideyuki; Yamamoto, Satoshi; Iso, Hiroyuki; Tanaka, Akito; Nishizaki, Tomoyuki

    2006-01-23

    In the water-maze test, the linoleic acid derivative, 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) (1 mg/kg, intraperitoneally), significantly shortened the prolonged latency for accelerated-senescence-prone mice 8 (SAMP8), reaching a level similar to the latency for accelerated-senescence-resistant mice 1 (SAMR1) as control. In the open-field test to assess motor activity, it was confirmed that the DCP-LA effect is not due to increased motor activity. In the passive avoidance test to assess fear memory, DCP-LA had no effect on the latency of acquisition and retention for SAMP8. The results of the present study, thus, suggest that DCP-LA could improve age-related learning impairment by enhancing cognitive functions.

  16. Strecker degradation of amino acids promoted by a camphor-derived sulfonamide.

    Science.gov (United States)

    Carvalho, M Fernanda N N; Ferreira, M João; Knittel, Ana S O; Oliveira, Maria da Conceição; Costa Pessoa, João; Herrmann, Rudolf; Wagner, Gabriele

    2016-01-01

    A camphor-derived sulfonimine with a conjugated carbonyl group, oxoimine 1 (O2SNC10H13O), reacts with amino acids (glycine, L-alanine, L-phenylalanine, L-leucine) to form a compound O2SNC10H13NC10H14NSO2 (2) which was characterized by spectroscopic means (MS and NMR) and supported by DFT calculations. The product, a single diastereoisomer, contains two oxoimine units connected by a -N= bridge, and thus has a structural analogy to the colored product Ruhemann´s purple obtained by the ninhydrin reaction with amino acids. A plausible reaction mechanism that involves zwitterions, a Strecker degradation of an intermediate imine and water-catalyzed tautomerizations was developed by means of DFT calculations on potential transition states. PMID:27340465

  17. Amino-modified tetraphenylethene derivatives as nucleic acid stain: relationship between the structure and sensitivity.

    Science.gov (United States)

    Xu, Li; Zhu, Zece; Wei, Danqing; Zhou, Xiang; Qin, Jingui; Yang, Chuluo

    2014-10-22

    A series of new amino-functionalized tetraphenylethene (TPE) derivatives were designed and synthesized to study the effect of molecular structures on the detection of nucleic acid. Contrastive studies revealed that the number of binding groups, the length of hydrophobic linking arm and the configuration of TPE molecule all play important roles on the sensitivity of the probes in nucleic acid detection. Z-TPE3 with two binding amino groups, long linking arms, and cis configuration was found to be the most sensitive dye in both solution and gel matrix. Z-TPE3 is able to stain dsDNA with the lowest amount of 1 ng and exclusively stain 40 ng of short oligonucleotide with only 10 nt. This work is of important significance for the further design of TPE probes as biosensors with higher sensitivity. PMID:25279446

  18. N-( p-Ethynylbenzoyl) derivatives of amino acid and dipeptide methyl esters - Synthesis and structural study

    Science.gov (United States)

    Eißmann, Frank; Weber, Edwin

    2011-11-01

    A series of N-( p-ethynylbenzoyl) derivatives ( 1-4) of the amino acids glycine and L-alanine as well as the dipeptides glycylglycine and L-alanylglycine has been synthesized via a two-step reaction sequence including the reaction of an appropriate N-( p-bromobenzoyl) precursor with trimethylsilylacetylene followed by deprotection of the trimethylsilyl protecting group, respectively. X-ray crystal structures of the amino acid and dipeptide methyl esters 1-4 are reported. The amide and peptide bonds within each molecular structure are planar and adopt the trans-configuration. The packing structures are governed by N sbnd H⋯O interactions leading to the formation of characteristic strand motifs. Further stabilization results from weaker C sbnd H⋯O and C sbnd H⋯π contacts.

  19. Wittig reaction (with ethylidene triphenylphosphorane) of oxo-hydroxy derivatives of 5β-cholanic acid: Hydrophobicity, haemolytic potential and capacity of derived ethylidene derivatives for solubilisation of cholesterol.

    Science.gov (United States)

    Poša, Mihalj; Bjedov, Srđan; Sebenji, Ana; Sakač, Marija

    2014-08-01

    Bile acid salts are biosurfactants which form mixed micelles with phospholipids in vertebrates. These mixed micelles are suitable for solubilisation of cholesterol. For therapeutic purposes some bile acid salts as sodium ursocholate are used. However, bile acid anions possess low capacity for solubilisation of cholesterol. Thus, synthesis of more hydrophobic and less membranotoxic bile acid derivatives is of the great interest. In this paper Wittig reaction between ethylidene triphenylphosphorane and different bile acids oxo derivatives is examined. Wittig reaction of bile acids has not been studied much. C12 oxo group is inert in this reaction. If Wittig reaction happens on C7 oxo group stereospecifically E ethylidene stereoisomer is obtained, while the same reaction on C3 oxo group leads to more reactive not sterospecific product. In this paper stereochemical course of investigated Wittig reactions is thoroughly analysed. Hydrophobicity of derived products is determined over the temperature (T) dependence on retention coefficients (k) in reversed phase high resolution chromatography. Using method of principle components on k=f(T) matrix it is found that values of first principle components best describe hydrophobicity of analysed bile acids, while the second principal component is responsible for their hydrophilicity. By in silico molecular descriptors: valence connectivity index of order 3 (X3v) and packing density index (PDI), linear regression equations are obtained that can be used to predict hydrophobicity (over retention coefficient) of bile acids that belong to set of more congeneric groups. Membranotoxicity is determined by haemolytic potential. Monoethylidene derivatives of bile acids (in the form of anions) have lower membranotoxicity than deoxycholic acids anion. Sodium salt of deoxycholic acid 7-ethylidene derivative has 11% greater capacity for solubilisation of cholesterol monohydrate than sodium salt of deoxycholic acid. PMID:24819990

  20. Arachidonic Acid Derivatives and Their Role in Peripheral Nerve Degeneration and Regeneration

    Directory of Open Access Journals (Sweden)

    Carlos Rodrigo Camara-Lemarroy

    2012-01-01

    Full Text Available After peripheral nerve injury, a process of axonal degradation, debris clearance, and subsequent regeneration is initiated by complex local signaling, called Wallerian degeneration (WD. This process is in part mediated by neuroglia as well as infiltrating inflammatory cells and regulated by inflammatory mediators such as cytokines, chemokines, and the activation of transcription factors also related to the inflammatory response. Part of this neuroimmune signaling is mediated by the innate immune system, including arachidonic acid (AA derivatives such as prostaglandins and leukotrienes. The enzymes responsible for their production, cyclooxygenases and lipooxygenases, also participate in nerve degeneration and regeneration. The interactions between signals for nerve regeneration and neuroinflammation go all the way down to the molecular level. In this paper, we discuss the role that AA derivatives might play during WD and nerve regeneration, and the therapeutic possibilities that arise.

  1. Arachidonic Acid Derivatives and Their Role in Peripheral Nerve Degeneration and Regeneration

    Science.gov (United States)

    Camara-Lemarroy, Carlos Rodrigo; Gonzalez-Moreno, Emmanuel Irineo; Guzman-de la Garza, Francisco Javier; Fernandez-Garza, Nancy Esthela

    2012-01-01

    After peripheral nerve injury, a process of axonal degradation, debris clearance, and subsequent regeneration is initiated by complex local signaling, called Wallerian degeneration (WD). This process is in part mediated by neuroglia as well as infiltrating inflammatory cells and regulated by inflammatory mediators such as cytokines, chemokines, and the activation of transcription factors also related to the inflammatory response. Part of this neuroimmune signaling is mediated by the innate immune system, including arachidonic acid (AA) derivatives such as prostaglandins and leukotrienes. The enzymes responsible for their production, cyclooxygenases and lipooxygenases, also participate in nerve degeneration and regeneration. The interactions between signals for nerve regeneration and neuroinflammation go all the way down to the molecular level. In this paper, we discuss the role that AA derivatives might play during WD and nerve regeneration, and the therapeutic possibilities that arise. PMID:22997489

  2. Evolution in medicinal chemistry of ursolic acid derivatives as anticancer agents.

    Science.gov (United States)

    Chen, Haijun; Gao, Yu; Wang, Ailan; Zhou, Xiaobin; Zheng, Yunquan; Zhou, Jia

    2015-03-01

    Currently, there is a renewed interest in common dietaries and plant-based traditional medicines for the prevention and treatment of cancer. In the search for potential anticancer agents from natural sources, ursolic acid (UA), a pentacyclic triterpenoid widely found in various medicinal herbs and fruits, exhibits powerful biological effects including its attractive anticancer activity against various types of cancer cells. However, the limited solubility, rapid metabolism and poor bioavailability of UA restricted its further clinical applications. In the past decade, with substantial progress toward the development of new chemical entities for the treatment of cancer, numerous UA derivatives have been designed and prepared to overcome its disadvantages. Despite extensive effort, discovery of effective UA derivatives has so far met with only limited success. This review summarizes the current status of the structural diversity and evolution in medicinal chemistry of UA analogues and provides a detailed discussion of future direction for further research in the chemical modifications of UA.

  3. Synthesis and Anti-tumor Activity of Novel Glycyrrhetinic Acid Derivatives

    Institute of Scientific and Technical Information of China (English)

    MENG Yan-qiu; DING Jia-qi; LIU Yuan; NIE Hui-hui; GUAN Sai; ZOU Chao; ZHAO Na; CHEN Hong; CAO Bo

    2012-01-01

    Twenty-five derivatives of glycyrrhetinic acid(GA)modified on the A-ring,at C30 and C11 positions were synthesized.Their in vitro cytotoxicity against various cancer cell lines[henrietta lacks strain of cancer cells(HeLa),human hepatocellular liver carcinoma cells(HepG2)and human gastric carcinoma cells(BGC-823)]was evaluated by standard MTT[3-(4,5-dimethyl-2-thiazol-yl)-2,5-diphenyl-2H-tetrazolium bromide]assay.All the tested derivatives were found to have stronger cell growth inhibitory than their parent compound GA.Among them,compounds 3a,5a,and 8d have similar activity on HeLa cell line,and compound 8a has similar activity on HeLa,HepG2 and BGC-823 cell lines as Gefitinib.

  4. Salt-inducible promoter derivable from a lactic acid bacterium, and its use in a lactic acid bacterium for production of a desired protein

    NARCIS (Netherlands)

    Sanders, Jan Willem; Kok, Jan; Venema, Gerard; Ledeboer, Adrianus Marinus

    1998-01-01

    The invention provides a salt-inducible promoter present in SEQ ID NO: 10 and derivable from a lactic acid bacterium in isolation from the coding sequence normally controlled by said promoter in a wild-type lactic acid bacterium, with modifications and important parts thereof. Also provided are a re

  5. Green Synthesis and Urease Inhibitory Activity of Spiro-Pyrimidinethiones/Spiro-Pyrimidinones-Barbituric Acid Derivatives.

    Science.gov (United States)

    Mohammadi Ziarani, Ghodsi; Asadi, Shima; Faramarzi, Sakineh; Amanlou, Massoud

    2015-01-01

    Sulfonic acid functionalized SBA-15 (SBA-Pr-SO3H) with pore size 6 nm as an efficient heterogeneous nanoporous solid acid catalyst exhibited good catalytic activity in the Biginelli-like reaction in the synthesis of spiroheterobicyclic rings with good yield and good recyclability. Spiro-pyrimidinethiones/spiro-pyrimidinones-barbituric acid derivatives were synthesized in a simple and efficient method using the one-pot three-component reaction of a cyclic 1,3- dicarbonyl compounds (barbituric acid), an aromatic aldehyde and urea or thiourea in the presence of nanoporous silica SBA-Pr-SO3H under solvent free conditions. Urease inhibitory activity of spiro compounds were tested against Jack bean urease using Berthelot alkaline phenol-hypochlorite method. Five of 13 compounds were inhibitor and two of them were enzyme activators. Analysis of the docking results showed that, in most of the spiro molecules, one of the carbonyl groups is coordinated with both nickel atoms, while the other one is involved in the formation of hydrogen bonds with important active-site residues. The effect of inserting two methyl groups on N atoms of barbiturate ring, S substituted, ortho, meta and para substituted compounds were investigated too. PMID:26664377

  6. Recent progress in electrochemical biosensors based on phenylboronic acid and derivatives.

    Science.gov (United States)

    Anzai, Jun-Ichi

    2016-10-01

    This review provides an overview of recent progress made in the development of electrochemical biosensors based on phenylboronic acid (PBA) and its derivatives. PBAs are known to selectively bind 1,2- and 1,3-diols to form negatively charged boronate esters in neutral aqueous media and have been used to construct electrochemical glucose sensors because of this selective binding. PBA-modified metal and carbon electrodes have been widely studied as voltammetric and potentiometric glucose sensors. In some cases, ferroceneboronic acid or ferrocene-modified phenylboronic acids are used as sugar-selective redox compounds. Another option for sensors using PBA-modified electrodes is potentiometric detection, in which the changes in surface potential of the electrodes are detected as an output signal. An ion-sensitive field effect transistor (FET) has been used as a signal transducer in potentiometric sensors. Glycoproteins, such as glycated hemoglobin (HbA1c), avidin, and serum albumin can also be detected by PBA-modified electrodes because they contain hydrocarbon chains on the surface. HbA1c sensors are promising alternatives to enzyme-based glucose sensors for monitoring blood glucose levels over the preceding 2-3months. In addition, PBA-modified electrodes can be used to detect a variety of compounds including hydroxy acids and fluoride (F(-)) ions. PBA-based F(-) ion sensors may be useful if reagentless sensors can be developed. PMID:27287174

  7. Uptake of acidic and basic sugar derivatives in Lemna gibba G1

    Energy Technology Data Exchange (ETDEWEB)

    Sanz, A.; Ullrich, C.I. (Universidad de Valencia (Spain) Institut fuer Botanik, Darmstadt (West Germany))

    1989-08-01

    The uptake of acidic and basic sugar derivatives in Lemna gibba L. was studied. Uronic acids applied to the experimental solution induced a small decrease of the membrane potential. After incubation of the plants in a 0.1 millimolar solution of these substrates, no decrease in the concentration of reducing groups in the external solution was detected. Respiration increased by 31% with 50 millimolar galacturonic acid, whereas no effect was found with the same concentration of glucuronic acid. Glucosamine caused a considerable concentration-dependent membrane depolarization. ({sup 14}C)glucosamine uptake followed Michaelis-Menten kinetics together with a linear component. Influx of this substrate was inhibited by glucose but the type of competition could not be clearly distinguished. Glucosamine, 50 millimolar, inhibited the respiration rate by 30%. The glucosamine uptake was pH-dependent, with maximum uptake at around pH 7. Lack of enhancement of uptake by low pH as well as the permanent membrane depolarization suggest a uniport mechanism for the charged species of the substrate and an electroneutral diffusion of the uncharged species.

  8. Production of fumaric acid from biodiesel-derived crude glycerol by Rhizopus arrhizus.

    Science.gov (United States)

    Zhou, Yuqing; Nie, Kaili; Zhang, Xin; Liu, Shihong; Wang, Meng; Deng, Li; Wang, Fang; Tan, Tianwei

    2014-07-01

    This work investigated the capability of Rhizopus arrhizus to assimilate biodiesel-derived crude glycerol and convert it into fumaric acid. After optimizing the initial glycerol concentration, spore inoculum and yeast extract concentration, smaller pellets (0.7 mm) and higher biomass (3.11 g/L) were obtained when R. arrhizus grew on crude glycerol. It was found that crude glycerol was more suitable than glucose for smaller R. arrhizus pellet forming. When 80 g/L crude glycerol was used as carbon source, the fumaric acid production of 4.37 g/L was obtained at 192 h. With a highest concentration of 22.81 g/L achieved in the co-fermentation of crude glycerol (40 g/L) and glucose (40 g/L) at 144 h, the fumaric acid production was enhanced by 553.6%, compared to the fermentation using glycerol (80 g/L) as sole carbon source. Moreover, the production cost of fumaric acid in co-fermentation was reduced by approximately 14% compared to glucose fermentation. PMID:24787316

  9. N-Hydroxypyrazolyl glycine derivatives as selective N-methyl-D-aspartic acid receptor ligands

    DEFF Research Database (Denmark)

    Clausen, Rasmus Prætorius; Christensen, Caspar; Hansen, Kasper Bø;

    2008-01-01

    glycine (NHP5G) derivatives are selectively recognized by N-methyl- d-aspartic acid (NMDA) receptors and that the ( R)-enantiomers are preferred. Moreover, several of the compounds are able to discriminate between individual subtypes among the NMDA receptors, providing new pharmacological tools. For......A series of analogues based on N-hydroxypyrazole as a bioisostere for the distal carboxylate group of aspartate have been designed, synthesized, and pharmacologically characterized. Affinity studies on the major glutamate receptor subgroups show that these 4-substituted N-hydroxypyrazol-5-yl...

  10. Visible-Light-Induced Decarboxylative Functionalization of Carboxylic Acids and Their Derivatives.

    Science.gov (United States)

    Xuan, Jun; Zhang, Zhao-Guo; Xiao, Wen-Jing

    2015-12-21

    Visible-light-induced radical decarboxylative functionalization of carboxylic acids and their derivatives has recently received considerable attention as a novel and efficient method to create CC and CX bonds. Generally, this visible-light-promoted decarboxylation process can smoothly occur under mild reaction conditions with a broad range of substrates and an excellent functional-group tolerance. The radical species formed from the decarboxylation step can participate in not only single photocatalytic transformations, but also dual-catalytic cross-coupling reactions by combining photoredox catalysis with other catalytic processes. Recent advances in this research area are discussed herein. PMID:26509837

  11. Synthesis and Structural Characterization of 1- and 2-Substituted Indazoles: Ester and Carboxylic Acid Derivatives

    OpenAIRE

    Isabel Bento; Teresa Duarte, M.; M. João M. Curto; Inês F. Antunes; Hélène Ramos; Fátima C. Teixeira

    2006-01-01

    A series of indazoles substituted at the N-1 and N-2 positions with ester-containing side chains -(CH2)nCO2R of different lengths (n = 0-6, 9, 10) are described.Nucleophilic substitution reactions on halo esters (X(CH2)nCO2R) by 1H-indazole inalkaline solution lead to mixtures of N-1 and N-2 isomers, in which the N-1 isomerpredominates. Basic hydrolysis of the ester derivatives allowed the synthesis of thecorresponding indazole carboxylic acids. All compounds were fully characterised bymultin...

  12. Further exploration of antimicrobial ketodihydronicotinic acid derivatives by multiple parallel syntheses

    DEFF Research Database (Denmark)

    Laursen, Jane B.; Nielsen, Janne; Haack, T.;

    2006-01-01

    synthetic manner and these were examined in vitro for their antimicrobial potential. Several compounds demonstrated significant broad-spectrum activity against clinically derived bacterial strains but previously known 1-(2,4-difluorophenyl)-6-(4-dimethylaminophenyl)-4-pyridone-3-carboxylic acid (7) remained...... the most potent compound in this class. Cross-resistance with ciprofloxacin supported a commonality of mode of action. Permiabilization of Escherichia coli cells by polymyxin B significantly enhanced potency with these agents suggesting that poor cellular uptake was primarily responsible...

  13. Oxidation of some disubstituted anisole derivatives with ceric perchlorate in perchloric acid solution

    International Nuclear Information System (INIS)

    The influence of concentration of particular reagents on the kinetics of Ce(IV) reduction by 2,6-dimethyl and 3,5-dimethyl-anisole as well as 2-methoxy-5-methyl- and 4-methoxy-2-methyl-aniline in perchloric acid solution was investigated, establishing the stoichiometry of these processes. Some intermediate products - macromolecular, derivatives of p-benzoquinone and 4,4'-diphenoquinone - were separated and identified. The effects of substituents and the conditions of performed oxidation processes on the kind and yields of the resultant products were considered. (author). 22 refs, 1 fig., 1 tab

  14. Synthesis and Antitumor Activity of Amino Acid Ester Derivatives Containing 5-Fluorouracil

    Directory of Open Access Journals (Sweden)

    Jing Xiong

    2009-08-01

    Full Text Available A series of amino acid ester derivatives containing 5-fluorouracil were synthesized using 1-ethyl-3-(3-dimethylaminopropylcarbodiimide hydrochloride (EDC•HCl and N-hydroxybenzotriazole (HOBt as a coupling agent. The structures of the products were assigned by NMR, MS, IR etc. The in vitro antitumor activity tests against leukaemia HL-60 and liver cancer BEL-7402 indicated that (R-ethyl 2-(2-(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H-ylacetamido-3-(4-hydroxyphenyl propanoate showed more inhibitory effect against BEL-7402 than 5-FU.

  15. Synthesis and Biological Activity of Arylspiroborate Salts Derived from Caffeic Acid Phenethyl Ester

    Directory of Open Access Journals (Sweden)

    Martin J. G. Hébert

    2015-01-01

    Full Text Available Two novel boron compounds containing caffeic acid phenethyl ester (CAPE derivatives have been prepared and characterized fully. These new compounds and CAPE have been investigated for potential antioxidant and antimicrobial properties and their ability to inhibit 5-lipoxygenase and whether chelation to boron improves their biological activity. Sodium salt 4 was generally more active than ammonium salt 5 in the biological assays and surpassed the radical scavenging ability of CAPE. Compounds 4 and 5 were more active than CAPE and Zileuton in human polymorphonuclear leukocytes. These results clearly show the effectiveness of the synthesized salts as transporter of CAPE.

  16. Polycarboxylate derivative of -amino acid as growth modifier of sulphide minerals

    Indian Academy of Sciences (India)

    Harjyoti Thakuria; Gopal Das

    2011-02-01

    Construction of modified inorganic mineral with controlled mineralization analogues of those produced by nature is now of current interest for understanding the mechanism of the in vivo biomineralization processes, as well as looking for fresh industrial and technological applications. Low-molecular-weight chiral polycarboxylate ligands derived fromnaturally occurring -\\alpha-amino acids have been used asmodel systems to study the effect of small organic matrix on crystal growth modification. The sulphide minerals are characterized by PXRD, FT–IR and SEM. Furthermore, the optical properties of these minerals have been characterized by UV-Vis and photoluminescence (PL) spectra.

  17. Synthesis of 6-sulfamoyl-4-oxoquinoline-3-carboxylic acid derivatives as integrase antagonists with anti-HIV activity

    Institute of Scientific and Technical Information of China (English)

    Zai Gang Luo; Cheng Chu Zeng; Lei Fu Yang; Hong Qiu He; Cun Xin Wang; Li Ming Hu

    2009-01-01

    A series of novel 6-sulfamoyl-4-oxoquinoline-3-earboxylic acids derivatives have been synthesized and screened for HIV integrase inhibition activity. Their structures were confirmed by ESI-MS, 1H NMR and 13C NMR.

  18. The marine sponge-derived polyketide endoperoxide plakortide F acid mediates its antifungal activity by interfering with calcium homeostasis

    Science.gov (United States)

    Plakortide F acid (PFA) is a marine-derived polyketide endoperoxide exhibiting strong inhibitory activity against several clinically important fungal pathogens. In the present study, transcriptional profiling coupled with mutant and biochemical analyses were conducted using the model organism Sacch...

  19. Synthesis, characterization and biological evaluation of N-ferrocenylmethyl amino acid benzene carboxamide derivatives and N-ferrocenyl benzoyl amino alkane derivatives as anti-cancer agents.

    OpenAIRE

    Butler, William E.

    2012-01-01

    The aim of this research was to explore the structure-activity relationship (SAR) of ferrocenyl-bioconjugates. A series of N-(ferrocenylmethylamino acid)-fluorinated-benzene carboxamide derivatives and a series of N-(ferrocenyl)-benzoyl-aminoalkane derivatives have been synthesised, structurally characterised and biologically evaluated for their anti-proliferative activity on various cancer cell lines, principally, the (estrogen receptor positive) MCF-7 breast cancer cell line. The anti-c...

  20. Isolation, modification, and aldose reductase inhibitory activity of rosmarinic acid derivatives from the roots of Salvia grandifolia.

    Science.gov (United States)

    Kang, Jie; Tang, Yanbo; Liu, Quan; Guo, Nan; Zhang, Jian; Xiao, Zhiyan; Chen, Ruoyun; Shen, Zhufang

    2016-07-01

    To find aldose reductase inhibitors, two previously unreported compounds, grandifolias H and I, and five known compounds, including rosmarinic acid and rosmarinic acid derivatives, were isolated from the roots of Salvia grandifolia. A series of rosmarinic acid derivatives was obtained from rosmarinic acid using simple synthetic methods. The aldose reductase inhibitory activity of the isolated and synthesized compounds was assessed. Seven of the tested compounds showed moderate aldose reductase inhibition (IC50=0.06-0.30μM). The structure-activity relationship of aldose reductase inhibitory activity of rosmarinic acid derivatives was discussed for the first time. This study provided useful information that will facilitate the development of aldose reductase inhibitors. PMID:27233987

  1. [Study of pantothenic acid derivatives as cardiac protectors in a model of experimental ischemia and reperfusion of the isolated heart].

    Science.gov (United States)

    Kumerova, A O; Utno, L Ia; Lipsberga, Z E; Shkestere, I Ia

    1992-04-01

    An isolated heart model with experimental ischemia and reperfusion was used to show effective decrease in lactate, increase in ATP content and prevention of conjugated dienes accumulation in the myocardium by derivatives of pantothenic acid: panthenol (9.0 mg/kg), calcium pantothenate (15.6 mg/kg) and by these ones applied simultaneously as ingredients of perfusate (25 microM) in postischemic period. In that way derivatives of pantothenic acid should be regarded as cardiac protectors. PMID:1391892

  2. Hydrolysis and rearrangement of phthalamic acid derivatives and assessment of their potential as prodrug forms for amines

    DEFF Research Database (Denmark)

    Bundgaard, H; Steffansen, B

    1990-01-01

    ) and various other N-alkyl and N-aryl substituted phthalamic acid derivatives were examined with the primary aim of assessing their degradation rate at physiological pH. Whereas the compounds I and II were indeed found to be easily degraded in neutral aqueous solutions, the degradation was not due....... It is concluded that phthalamic acid derivatives are too stable chemically and enzymatically to be considered as prodrug forms for primary or secondary amines....

  3. Modification of the cellulosic component of hemp fibers using sulfonic acid derivatives: Surface and thermal characterization.

    Science.gov (United States)

    George, Michael; Mussone, Paolo G; Bressler, David C

    2015-12-10

    The aim of this study was to characterize the surface, morphological, and thermal properties of hemp fibers treated with two commercially available, inexpensive, and water soluble sulfonic acid derivatives. Specifically, the cellulosic component of the fibers were targeted, because cellulose is not easily removed during chemical treatment. These acids have the potential to selectively transform the surfaces of natural fibers for composite applications. The proposed method proceeds in the absence of conventional organic solvents and high reaction temperatures. Surface chemical composition and signature were measured using gravimetric analysis, X-ray photoelectron spectroscopy (XPS) and Fourier transform infra-red spectroscopy (FTIR). XPS data from the treated hemp fibers were characterized by measuring the reduction in O/C ratio and an increase in abundance of the C-C-O signature. FTIR confirmed the reaction with the emergence of peaks characteristic of disubstituted benzene and amino groups. Grafting of the sulfonic derivatives resulted in lower surface polarity. Thermogravimetric analysis revealed that treated fibers were characterized by lower percent degradation between 200 and 300 °C, and a higher initial degradation temperature.

  4. Effects of Citric and Lactic Acid on the Reduction of Deoxynivalenol and Its Derivatives in Feeds

    Science.gov (United States)

    Humer, Elke; Lucke, Annegret; Harder, Hauke; Metzler-Zebeli, Barbara U.; Böhm, Josef; Zebeli, Qendrim

    2016-01-01

    Exposure to mycotoxin-contaminated feeds represents a serious health risk. This has necessitated the need for the establishment of practical methods for mycotoxin decontamination. This study investigated the effects of citric acid (CA) and lactic acid (LA) on common trichothecene mycotoxins in feeds contaminated with Fusarium mycotoxins. Contaminated feed samples were processed either with 5% CA or 5% LA solutions in a ratio of 1:1.2 (w/v) for 5, 24, or 48 h, and analyzed for multiple mycotoxin metabolites using a liquid chromatography–tandem mass spectrometric method. The analyses showed that treating the feed with CA and LA lowered the concentration of deoxynivalenol (DON), whereby 5% LA lowered the original DON concentration in the contaminated feed samples by half, irrespective of the processing time. Similar lowering effects were observed for the concentrations of 15Ac-DON, 5-hydroxyculmorin, and sambucinol. The concentration of nivalenol was only lowered by the LA treatment. In contrast, CA and LA treatments showed no or only small effects on the concentration of several mycotoxins and their derivatives, including zearalenone, fumonisins, and culmorin. In conclusion, the present results indicate that the use of 5% solutions of LA and CA might reduce the concentration of common trichothecene mycotoxins, especially DON and its derivate 15Ac-DON. However, further research is required to determine the effect on overall toxicity and to identify the underlying mechanisms. PMID:27690101

  5. Synthesis and Application of Phenyl Nitrone Derivatives as Acidic and Microbial Corrosion Inhibitors

    Directory of Open Access Journals (Sweden)

    Shijun Chen

    2015-01-01

    Full Text Available Nitrone has drawn great attention due to its wide applications as a 1,3-dipole in heterocyclic compounds synthesis and the bioactivities. With the special structure, nitrone can also be used as ligand in inorganic chemistry. Based on the current research, the nitrones are anticipated to be effective inhibitors against acidic and microbial corrosion. The aim of this work is to investigate the inhibitory action of nitrones. In this work, a series of phenyl nitrone derivatives (PN was synthesized and used as acidic and microbial corrosion inhibitors. The results indicate that several compounds show moderate to high inhibition efficiency (IE in 3% HCl. Accompanied with HMTA or BOZ, the IEs greatly increase, and the highest efficiency of 98.5% was obtained by using PN4 + BOZ. Investigation of the antibacterial activity against oilfield microorganism shows that the nitrone derivatives can inhibit SRB, IB, and TGB with moderate to high efficiency under 1,000 mg/L, which makes them potential to be used as bifunctional oilfield chemicals.

  6. Synthesis, spectroscopic characterizations, crystal structures and DFT studies of nalidixic acid carbonyl hydrazones derivatives

    Science.gov (United States)

    Bergamini, F. R. G.; Ribeiro, M. A.; Lancellotti, M.; Machado, D.; Miranda, P. C. M. L.; Cuin, A.; Formiga, A. L. B.; Corbi, P. P.

    2016-09-01

    This article describes the synthesis and characterization of the 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbohydrazide (hzd) and six carbonyl hydrazones derivatives of the nalidixic with 1H-pyrrol-2-ylmethylidene (hpyrr), 1H-imidazol-2-ylmethylidene (h2imi), pyridin-2-ylmethylidene (h2py), pyridin-3-ylmethylidene (h3py), pyridin-4-ylmethylidene(h4py) and (2-hydroxyphenyl)methylidene (hsali). The carbonyl hydrazones were characterized by elemental and ESI-QTOF-MS analyses, IR and detailed NMR spectroscopic measurements. The 2D NMR experiments allowed the unambiguous assignment of the hydrogen, carbon and nitrogen atoms, which have not been reported for nalidixic acid carbonyl hydrazone derivatives so far. Crystal structures of hzd and the new carbonyl hydrazones h2imi, hpyrr and h3py were determined by X-ray diffraction studies. Although the synthesis of hzd was reported decades ago, the hzd crystal structure have not been reported yet. Geometric optimizations of all the characterized structures were performed with the aid of DFT studies. Despite the fact that the hydrazones with 2-pyridine carboxylic acid (h2py) and salicyl aldehyde (hsali) were already reported by literature, a detailed spectroscopic study followed by DFT studies are also reported for such compounds in this manuscript. Antimicrobial studies of the compounds are also presented.

  7. Synthesis and Antiproliferative Activity of Some Novel Triazole Derivatives from Dehydroabietic Acid

    Directory of Open Access Journals (Sweden)

    Mariano Walter Pertino

    2014-02-01

    Full Text Available Dehydroabietic acid (DHA is a naturally occurring diterpene with different and relevant biological activities. Previous studies have shown that some DHA derivatives display antiproliferative activity. However, the reported compounds did not include triazole derivatives. Starting from DHA (8,11,13-abietatrien-18-oic acid, and its alcohol dehydroabietinol (8,11,13-abietatrien-18-ol, four alkyl esters were prepared. The alkyl terpenes were treated with different aromatic azides to synthesize hybrid compounds using click chemistry. Some 16 new DHA hybrids were thus synthesized and their structures were confirmed by spectroscopic and spectrometric means. The antiproliferative activity of the new compounds was assessed towards human cell lines, namely normal lung fibroblasts (MRC-5, gastric epithelial adenocarcinoma (AGS, lung cancer (SK-MES-1 and bladder carcinoma (J82 cells. Better antiproliferative effect was found for compound 5, with an IC50 of 6.1 μM and selectivity on SK-MES-1 cells. Under the same experimental conditions, the IC50 of etoposide, was 1.83 µM.

  8. Hypolipidemic effect of pantothenic acid derivatives in mice with hypothalamic obesity induced by aurothioglucose.

    Science.gov (United States)

    Naruta, E; Buko, V

    2001-10-01

    The hypolipidemic effects of pantothenic acid derivatives (phosphopantothenate, panthenol and pantethine) were studied in mice with hypothalamic obesity. Hypothalamic obesity in mice was induced by single injection of aurothioglucose (300 mg/kg body wt, i.p.). All the tested substances were administered during the last 10 days before decapitation (i.m., of dosage equivalent to 150 mg/kg body wt of phosphopantothenate). The studied substances inhibited the weight gain of the animals with hypothalamic obesity over the last 10 days of the experiment. The treatment with aurothioglucose increased food intake and mean body weight, blood glucose level; insulin, serum total cholesterol, triglyceride, the sum of LDL + VLDL and LDL-cholesterol concentration; triglyceride and cholesterol fractions in the liver; triglyceride and FFA content as well as lipoprotein lipase activity in adipose tissue of experimental mice. The administration of the assay compounds lowered food intake and mean body weight, insulin and glucose levels and decreased the content of triglycerides, total cholesterol and cholesterol esters in serum and adipose tissue as well as raised the activity of lipoprotein lipase in adipose tissue and serum lipolytic activity in obese mice. Among the compounds studied the reverse effect of panthenol was especially pronounced. The mechanism of hypolipidemic effects of pantothenic acid derivatives can be related to the reduced resistance to insulin and activation of lipolysis in serum and adipose tissue. PMID:11817109

  9. Toxicity of Some Cinnamic Acid Derivatives to Common Bean (Phaseolus vulgaris

    Directory of Open Access Journals (Sweden)

    Alexandra JITĂREANU

    2011-11-01

    Full Text Available Cinnamic acid derivatives are an important class of biologically active compounds, playing an important role in the plants’ development, but may also present a wide range of actions: antimicrobial, antioxidant, antiinflamatory, antitumoral. The present study investigated the toxicity of ten cinnamic acid derivatives on Phaseolus vulgaris, this being the first step in evaluating their pharmacotoxicological potential (usually, plant toxicity tests are used for ecotoxicity assessment, but they can also provide some useful general information about the toxic potential of a pharmaceutical substance to living organisms. The bean seeds were exposed to three different concentrations of each substance (28.6 μg/cm2, 57.3 μg/cm2, 114.6 μg/cm2. All the tests were conducted in Petri dishes, using an artificial substrate (Whatman filter paper impregnated with the investigated compounds. The analyzed elements were seedling length, root length, percentage of seeds that developed into seedlings, fresh seedling weight and the total polyphenols content. The tested compounds showed phytotoxic effects, inhibiting the growth of the plants and the biosynthesis of polyphenols as compared to the control. The substances with high logP values showed greater phytotoxic potential, but to establish an exact correlation between hydrophobicity and toxicity of the molecules a QSAR analysis must be further done.

  10. Synthesis of ino Acid Derived β-Cyclodextrins Used in Chiral Separation by Capillary Electrophoresis

    Institute of Scientific and Technical Information of China (English)

    戴荣继; 佟斌; 魏征; 顾峻岭; 邓玉林; 李明愉; 傅若农

    2004-01-01

    Six new kinds of ino acid derived β-cyclodextrins were synthesized to improve their water solubility and chiral separation properties. They are heptakis{2,6-di-O-[3-L-(1-isopropyl carboxyl methyl ino)-2-hydroxy propyl]}-β-cyclodextrin (i.e. L-Val-β-CD), heptakis{2,6-di-O-[3-L-(1-benzyl carboxyl methyl ino)-2-hydroxy propyl]}-β-cyclodextrin (i.e. L-Phe-β-CD), heptakis{2,6-di-O-[3-(D, L-1-benzyl carboxyl methyl ino)-2-hydroxy propyl]}-β-cyclodextrin (i.e. D,L-Phe-β-CD), heptakis{2,6-di-O-[3-(L-1-hydroxymethyl carboxyl methyl ino)-2-hydroxy propyl]}-β-cyclodextrin (i.e. L-Ser-β-CD), heptakis{2,6-di-O-[3-(L-1-carboxylmethyl carboxyl methyl ino)- 2-hydroxy propyl]}-β-cyclodextrin (i.e. L-Asp-β-CD), heptakis{2,6-di-O-[3-(L-2-carboxyl tetrethylene ino)-2-hydroxy propyl]}-β-cyclodextrin (i.e. L-Pro-β-CD). Their chemical structures were certified using FTIR and 1H NMR. Except for L-Phe-β-CD and D,L-Phe-β-CD, that are in soluble in water, the other ino acid derived β-CDs all have good water solubility. D,L-tyrosine and promethazine were baselinely separated by L-Val-β-CD in capillary electrophoresis.

  11. Rapid formation of β-allyl substituted isotetronic acid derivatives via Claisen rearrangement using a microfludic device

    Institute of Scientific and Technical Information of China (English)

    Xia Ping Ma; Zhi Ming Li; Quan Rui Wang

    2011-01-01

    The thermal Claisen rearrangement of O-allyl substituted isotetronic acids 1 was successfully carried out within a glass microreactor operated with temperature at 150 ℃ and a flow rate of 1 mL/h. The strategy provides an efficient alternative way to β-allyl substituted isotetronic acid derivatives 2 in high yields with much accelerated reaction speed.

  12. Gadolinium-DOTA enhanced MRI of painful osseous crises in children with sickle cell anemia

    International Nuclear Information System (INIS)

    In order to evaluate the role of gadolinium-DOTA enhanced MRI in the management of painful osseous crises in children with sickle cell anemia (SCA), nine children with SCA underwent MRI, bone scans and ultrasonographic studies during 11 osseous crises. Imaging findings were compared with the final diagnosis: three acute osteomyelitis (AO) and 16 acute infarcts (AI). MRI could not differentiate AO from AI. The appearance of severe AI was very misleading and was similar to the usual appearance of AO, including soft tissue changes, periosteal reaction and patterns of enhancement. Gadolinium-DOTA enhanced MRI was useful for determining the anatomic site and extent of AO or AI and for distinguishing between necrotic material, fluid collection and vascularized inflammatory tissue. It can also help to guide the aspiration of intraosseous, subperiosteal and soft tissue fluid collections. (orig.)

  13. Gadolinium-DOTA enhanced MRI of painful osseous crises in children with sickle cell anemia

    Energy Technology Data Exchange (ETDEWEB)

    Bonnerot, V. (Dept. of Pediatric Radiology, Hopital des Enfants Malades, 75 - Paris (France)); Sebag, G. (Dept. of Pediatric Radiology, Hopital des Enfants Malades, 75 - Paris (France)); Montalembert, M. de (Dept. of Pediatric Hematology, Hopital des Enfants Malades, 75 - Paris (France)); Wioland, M. (Dept. of Nuclear Medicine, Hopital Saint-Antoine, 75 - Paris (France)); Glorion, C. (Dept. of Orthopedics, Hopital des Enfants Malades, 75 - Paris (France)); Girot, R. (Dept. of Pediatric Hematology, Hopital des Enfants Malades, 75 - Paris (France)); Lallemand, D. (Dept. of Pediatric Radiology, Hopital des Enfants Malades, 75 - Paris (France))

    1994-04-01

    In order to evaluate the role of gadolinium-DOTA enhanced MRI in the management of painful osseous crises in children with sickle cell anemia (SCA), nine children with SCA underwent MRI, bone scans and ultrasonographic studies during 11 osseous crises. Imaging findings were compared with the final diagnosis: three acute osteomyelitis (AO) and 16 acute infarcts (AI). MRI could not differentiate AO from AI. The appearance of severe AI was very misleading and was similar to the usual appearance of AO, including soft tissue changes, periosteal reaction and patterns of enhancement. Gadolinium-DOTA enhanced MRI was useful for determining the anatomic site and extent of AO or AI and for distinguishing between necrotic material, fluid collection and vascularized inflammatory tissue. It can also help to guide the aspiration of intraosseous, subperiosteal and soft tissue fluid collections. (orig.)

  14. Amino acid esters substituted phosphorylated emtricitabine and didanosine derivatives as antiviral and anticancer agents.

    Science.gov (United States)

    Sekhar, Kuruva Chandra; Janardhan, Avilala; Kumar, Yellapu Nanda; Narasimha, Golla; Raju, Chamarthi Naga; Ghosh, S K

    2014-07-01

    Owing to the promising antiviral activity of amino acid ester-substituted phosphorylated nucleosides in the present study, a series of phosphorylated derivatives of emtricitabine and didanosine substituted with bioactive amino acid esters at P-atom were synthesized. Initially, molecular docking studies were screened to predict their molecular interactions with hemagglutinin-neuraminidase protein of Newcastle disease virus and E2 protein of human papillomavirus. The title compounds were screened for their antiviral ability against Newcastle disease virus (NDV) by their in ovo study in embryonated chicken eggs. Compounds 5g and 9c exposed well mode of interactions with HN protein and also exhibited potential growth of NDV inhibition. The remaining compounds exhibited better growth of NDV inhibition than their parent molecules, i.e., emtricitabine (FTC) and didanosine (ddI). In addition, the in vitro anticancer activity of all the title compounds were screenedagainst HeLa cell lines at 10 and 100 μg/mL concentrations. The compounds 5g and 9c showed an effective anticancer activity than that of the remaining title compounds with IC50 values of 40 and 60 μg/mL, respectively. The present in silico and in ovo antiviral and in vitro anticancer results of the title compounds are suggesting that the amino acid ester-substituted phosphorylated FTC and ddI derivatives, especially 5g and 9c, can be used as NDV inhibitors and anticancer agents for the control and management of viral diseases with cancerous condition. PMID:24789416

  15. Analysis of benzoic and cinnamic acid derivatives of some medicinal plants in Serbia

    Directory of Open Access Journals (Sweden)

    Đurđević L.

    2013-01-01

    Full Text Available Natural phenolics, which are ubiquitously distributed in plants, have been reported as functional factors in phytotherapy. We have examined phenolic compounds in the leaves and inflorescences of five significant medicinal plants of different plant families: Salvia officinalis (Lamiaceae; Achillea clypeolata (Asteraceae; Nymphaea alba (Nymphaeaceae; Rumex acetosella (Polygonaceae and Allium ursinum (Alliaceae. The examined species were rich in total phenolics (up to 30.88 mg/g dry weight. According to their total phenolics contents, the plants can be arranged in the following order: A. clypeolata>N. alba>S. officinalis>R. acetosella>A. ursinum. Free phenolics prevailed in all species in comparison to the bound forms (63.72-82.68% of total phenolics. The highest content of total free phenolics was measured in the tissues of A. clypeolata and N. alba, and the lowest in A. ursinum. Five phenolic acids were isolated and measured. p-Coumaric and ferulic acids as derivatives of cinnamic acid prevailed in the leaves of R. acetosella and A. ursinum (up to 4.81%. [Projekat Ministarstva nauke Republike Srbije, br. 173018

  16. Synthesis, Activity, and Docking Study of Novel Phenylthiazole-Carboxamido Acid Derivatives as FFA2 Agonists.

    Science.gov (United States)

    Ma, Liang; Wang, Taijin; Shi, Min; Fu, Ping; Pei, Heying; Ye, Haoyu

    2016-07-01

    Free fatty acid receptor 2 (FFA2), also known as GPR43, is activated by short-chain fatty acids (SCFAs) that are mainly produced by the gut microbiota through the fermentation of undigested carbohydrates and dietary fibers. FFA2 currently appears to be a potential target in the management of obesity, diabetes, inflammatory diseases, and cancer. In the study, a series of novel phenylthiazole-carboxamido acid derivatives has been synthesized and evaluated as potential orthosteric FFA2 ligands for the study of structure-activity relationships. Compound 6e was found to exhibit the twofold potent agonistic activity in the stable hFFA2-transfected CHO-K1 cells (EC50 = 23.1 μm) as that of positive control propionate (EC50 = 43.3 μm). We also reported the results of mutagenesis studies based on the crystal structure of hFFA1 bound to TAK-875 at 2.3 Å resolution to identify important residues for orthosteric agonist 6e inducing FFA2 activation. PMID:26808470

  17. DFT computational study on decarboxylation mechanism of salicylic acid and its derivatives in the anionic state

    Science.gov (United States)

    Gao, Lu; Hu, Yanying; Zhang, Huitu; Liu, Yanchun; Song, Zhidan; Dai, Yujie

    2016-07-01

    The mechanisms of the decarboxylation of salicylic acid anion and its ortho substituted derivatives in gas phase and aqueous solution have been investigated by B3LYP method of DFT theory using the 6-31++G (d,p) basis set. The decarboxylation process includes hydrogen transfers from hydroxyl to carboxyl group and from carboxyl to the α-C of the aryl ring. The mechanism suggested is a pseudo-unimolecular decomposition of the salicylic acid anion and the hydrogen transfer from carboxyl to the α-C of the aryl ring is the rate determining step. Compared with the decarboxylation process in gas phase, the energy barriers in aqueous solution approximately declined by 25%-31%with the water mediation of the hydrogen transfer from carboxyl to the α-C of the aryl ring. The effects of substituents at the ortho position on the decarboxylation process were also investigated. Both the electron donating CH3 and withdrawing group NO2 at the ortho position of carboxyl group can further reduce the reaction energy barriers of the decarboxylation of salicylic acid anions.

  18. Versatile Biodegradable Poly(ester amides Derived from α-Amino Acids for Vascular Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Pooneh Karimi

    2010-03-01

    Full Text Available Biodegradable poly(ester amide (PEA biomaterials derived from α-amino acids, diols, and diacids are promising materials for biomedical applications such as tissue engineering and drug delivery because of their optimized properties and susceptibility for either hydrolytic or enzymatic degradation. The objective of this work was to synthesize and characterize biodegradable PEAs based on the α-amino acids L-phenylalanine and L-methionine. Four different PEAs were prepared using 1,4-butanediol, 1,6-hexanediol, and sebacic acid by interfacial polymerization. High molecular weight PEAs with narrow polydispersity indices and excellent film-forming properties were obtained. The incubation of these PEAs in PBS and chymotrypsin indicated that the polymers are biodegradable. Human coronary artery smooth muscle cells were cultured on PEA films for 48 h and the results showed a well-spread morphology. Porous 3D scaffolds fabricated from these PEAs were found to have excellent porosities indicating the utility of these polymers for vascular tissue engineering.

  19. An efficient way to coupling amine with derivatives of steric N-Boc-pyrrolidine-2-carboxylic acid

    Institute of Scientific and Technical Information of China (English)

    Feng Zhi Liu; Hao Fang; Wen Fang Xu

    2007-01-01

    An efficient way to coupling amine with the derivatives of steric N-Boc-pyrrolidine-2-carboxylic acid was reported in this paper.We have found that the synthesis of derivatives is problematic with the commonly used DCC/HOBT method. As a substitute, the mixed anhydride method was adopted. A series of 6-(3-nitroguanidino)hexanamidopyrrolidine derivatives were prepared with this method.

  20. Lanthanide nitrates as Lewis acids in the one-pot synthesis of 1,2,4-oxadiazole derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Vale, Juliana A.; Faustino, Wagner M., E-mail: julianadqf@yahoo.com.br [Departamento de Quimica, Universidade Federal da Paraiba, Joao Pessoa, PB (Brazil); Zampieri, Davila de S.; Moran, Paulo J.S.; Rodrigues, Jose A.R. [Instituto de Quimica, Universidade Estadual de Campinas, SP (Brazil); Sa, Gilberto F. de [Departamento de Quimica Fundamental, CCEN, Universidade Federal de Pernambuco, Recife, PE (Brazil)

    2012-08-15

    In this work we report the use of lanthanide nitrates [Ln(NO{sub 3}){sub 3}] acting as catalyst in direct one pot synthesis of 3-benzoyl- and 3-acetyl-1,2,4-oxadiazoles derivatives from ketones, nitriles and nitric acid. This is the first example of one-pot synthesis of benzoyl- and acetyl 1,2,4-oxadiazoles derivatives preparation using acetophenones derivates with electron-donator groups. (author)

  1. Rheological and Biological Characteristics of Hyaluronic Acid Derivative Modified by Polyethylene Glycol

    Institute of Scientific and Technical Information of China (English)

    CHEN Jinghua; CHEN Jingtao; XU Zheng

    2008-01-01

    Hyaluronic acid (HA) was chemically modified by polyethylene glycol. Meanwhile,the dynamic mechanics properties of HA derivative and its viscoelastic changes were measured on 3ARES3 Rheometer (Japan) at 25 ℃. Dried cross-linked films of 10×10 mm2 were immersed in phosphate buffered saline(PBS: pH 7.4) at 37 ℃ with different time periods to measure its water content and in vitro degradation. Moreover, cell cultured solutions, which were in the different cultivation vesse with 1 mg/mL Solution of HA derivative as doing experimental sample for 2 d, 4 d and 7 d, were observed, respectively, by an inverted discrepancy microscope. The cell relative growth rate was analyzed with the SPSS10.0 mathematic statistic software. Based on the above experiments,structure-modified HA derivative can meet the requirements of biomaterials in view of rheological and degradation in vitro and cytotoxicity charactereistics from clinical medical aspect under this experiment conditions.

  2. The effect of short-chain fatty acids on human monocyte-derived dendritic cells.

    Science.gov (United States)

    Nastasi, Claudia; Candela, Marco; Bonefeld, Charlotte Menné; Geisler, Carsten; Hansen, Morten; Krejsgaard, Thorbjørn; Biagi, Elena; Andersen, Mads Hald; Brigidi, Patrizia; Ødum, Niels; Litman, Thomas; Woetmann, Anders

    2015-01-01

    The gut microbiota is essential for human health and plays an important role in the pathogenesis of several diseases. Short-chain fatty acids (SCFA), such as acetate, butyrate and propionate, are end-products of microbial fermentation of macronutrients that distribute systemically via the blood. The aim of this study was to investigate the transcriptional response of immature and LPS-matured human monocyte-derived DC to SCFA. Our data revealed distinct effects exerted by each individual SCFA on gene expression in human monocyte-derived DC, especially in the mature ones. Acetate only exerted negligible effects, while both butyrate and propionate strongly modulated gene expression in both immature and mature human monocyte-derived DC. An Ingenuity pathway analysis based on the differentially expressed genes suggested that propionate and butyrate modulate leukocyte trafficking, as SCFA strongly reduced the release of several pro-inflammatory chemokines including CCL3, CCL4, CCL5, CXCL9, CXCL10, and CXCL11. Additionally, butyrate and propionate inhibited the expression of lipopolysaccharide (LPS)-induced cytokines such as IL-6 and IL-12p40 showing a strong anti-inflammatory effect. This work illustrates that bacterial metabolites far from the site of their production can differentially modulate the inflammatory response and generally provides new insights into host-microbiome interactions. PMID:26541096

  3. Synthesis and Insecticidal Activity of Novel Camptothecin Derivatives Containing Analogs of Chrysanthemic Acid Moieties

    Institute of Scientific and Technical Information of China (English)

    DENG Li; ZHANG Lan; CAO Li-dong; XIE Ru-liang; ZHANG Yan-ning; HE Wei-zhi; JIANG Hong-yun

    2014-01-01

    Creating high-efifcient and environment-friendly pesticides is very important to produce the pollution free agriculture food and maintain the balance of the survival environmental of the human being. According to reports, camptothecin (CPT) and its derivatives are now being explored as a class of botanical insecticide in agriculture due to its novel mode of action. In order to improve the insecticidal activity of CPT, ten novel camptothecin (1) and 10-hydroxycamptothecin (2) derivatives (1a, 1b, 1c, 1d, 1e;2a, 2b, 2c, 2d, 2e) were designed and synthesized via esteriifcation with analogs of chrysanthemic acid, which have outstanding insecticidal activity. The results showed that compound 2a exhibited potent antifeeding effect and the best contact toxicity among the target compounds against the third-instar larvae of beet armyworm, Spodoptera exigua Hübner. Compound 2a was also found to be the most effective cytotoxic compound to the tested insect cell lines, IOZCAS-Spex-II, which were established from the fat bodies of S. exigua. It was proposed that the 10-hydroxyl group in the camptothecin derivatives is a key factor for the antifeeding activity of a compound. The nature of the substituents was considered the major factor in determining the insecticidal activity of these compounds.

  4. Switch from antagonist to agonist after addition of a DOTA chelator to a somatostatin analog

    Energy Technology Data Exchange (ETDEWEB)

    Reubi, Jean Claude; Cescato, Renzo; Waser, Beatrice [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, PO Box 62, Berne (Switzerland); Erchegyi, Judit; Rivier, Jean E. [The Salk Institute for Biological Studies, The Clayton Foundation Laboratories for Peptide Biology, La Jolla, CA (United States)

    2010-08-15

    Peptide receptor targeting has become an increasingly attractive method to target tumors diagnostically and radiotherapeutically. Peptides linked to a variety of chelators have been developed for this purpose. They have, however, rarely been tested for their agonistic or antagonistic properties. We report here on a somatostatin antagonist that switched to an agonist upon coupling to a DOTA chelator. Two novel somatostatin analogs, 406-040-15 and its DOTA-coupled counterpart 406-051-20, with and without cold Indium labeling, were tested for their somatostatin receptor subtypes 1-5 (sst{sub 1}-sst{sub 5}) binding affinity using receptor autoradiography. Moreover, they were tested functionally for their ability to affect sst{sub 2} and sst{sub 3} internalization in vitro in HEK293 cells stably expressing the human sst{sub 2} or sst{sub 3} receptor, using an immunofluorescence microscopy-based internalization assay. All three compounds were characterized as pan-somatostatin analogs having a high affinity for all five sst. In the sst{sub 2} internalization assay, all three compounds showed an identical behavior, namely, a weak agonistic effect complemented by a weak antagonistic effect, compatible with the behavior of a partial agonist. Conversely, in the sst{sub 3} internalization assay, 406-040-15 was a full antagonist whereas its DOTA-coupled counterpart, 406-051-20, with and without Indium labeling, switched to a full agonist. Adding the DOTA chelator to the somatostatin analog 406-040-15 triggers a switch at sst{sub 3} receptor from an antagonist to an agonist. This indicates that potential radioligands for tumor targeting should always be tested functionally before further development, in particular if a chelator is added. (orig.)

  5. PET/CT with 68Gallium-DOTA-peptides in NET: An overview

    Energy Technology Data Exchange (ETDEWEB)

    Ambrosini, Valentina [Department of Nuclear Medicine, Sant' Orsola-Malpighi University Hospital, Bologna (Italy); Campana, Davide; Tomassetti, Paola [Department of Internal Medicine, Sant' Orsola-Malpighi University Hospital, Bologna (Italy); Grassetto, Gaia [Department of Radiology, Nuclear Medicine, Medical Physics, Santa Maria della Misericordia Hospital, Via Tre Martiri 140, 45100 Rovigo (Italy); Rubello, Domenico, E-mail: domenico.rubello@ibero.it [Department of Radiology, Nuclear Medicine, Medical Physics, Santa Maria della Misericordia Hospital, Via Tre Martiri 140, 45100 Rovigo (Italy); Fanti, Stefano [Department of Nuclear Medicine, Sant' Orsola-Malpighi University Hospital, Bologna (Italy)

    2011-11-15

    In the present review article we presented the major technical innovations regarding the diagnosis of NET with PET/CT 68Ga-DOTA-peptides compounds over conventional radiologic and scintigraphic imaging, discussing both the different types of radiopharmaceuticals commercially available, trying to making a comparison on the possible advantages and drawbacks of these radiopharmaceuticals, and providing also some technical recommendations to the radiologists and nuclear physicians for using these new methodology in an appropriate manner in the clinical setting.

  6. Peptide-Targeted Nanoglobular Gd-DOTA Monoamide Conjugates for Magnetic Resonance Cancer Molecular Imaging

    OpenAIRE

    Tan, Mingqian; Wu, Xueming; Jeong, Eun-Kee; Chen, Qianjin; Lu, Zheng-Rong

    2010-01-01

    Effective imaging of cancer molecular biomarker is critical for accurate cancer diagnosis and prognosis. CLT1 peptide was observed to specifically bind to the fibrin-fibronectin complexes presented in tumor extracellular matrix. In this study, we synthesized and evaluated CLT1 peptide-targeted nanoglobular Gd-DOTA monoamide conjugates for magnetic resonance (MR) imaging of the fibrin-fibronectin complexes in tumor. The targeted nanoglobular contrast agents were prepared by conjugating peptide...

  7. Study of holmium (III) and yttrium(III) with DOTA complexes as candidates for radiopharmaceutical use

    Science.gov (United States)

    Ernestová, M.; Jedináková-Křížová, V.

    2003-01-01

    Reaction conditions for complexation of radionuclides with DOTA were studied using thinlayer chromatography (TLC), paper chromatography (PC) and potentiometry. It was found that all of the studied complexes can reach very high radiochemical yield about 95%. Optimal conditions for obtaining such high radiochemical yields are as follows: pH higher than 4 and the excess of chelating agent must be minimally 3∶1. Potentiometric study showed that the formation of complexes is characterised by very slow kinetics.

  8. Bioorthogonal chemistry for (68) Ga radiolabelling of DOTA-containing compounds.

    Science.gov (United States)

    Evans, Helen L; Carroll, Laurence; Aboagye, Eric O; Spivey, Alan C

    2014-04-01

    Copper-catalysed 'click' chemistry is a highly utilised technique for radiolabelling small molecules and peptides for imaging applications. The usefulness of these reactions falls short, however, when metal catalysis is not a practically viable route; such as when using metal chelates as radioligands. Here, we describe a method for carrying out 'click-type' radiochemistry in the presence of DOTA chelates, by combining (68) Ga radiolabelling techniques with well-established bioorthogonal reactions, which do not rely upon metal catalysis.

  9. Switch from antagonist to agonist after addition of a DOTA chelator to a somatostatin analog

    International Nuclear Information System (INIS)

    Peptide receptor targeting has become an increasingly attractive method to target tumors diagnostically and radiotherapeutically. Peptides linked to a variety of chelators have been developed for this purpose. They have, however, rarely been tested for their agonistic or antagonistic properties. We report here on a somatostatin antagonist that switched to an agonist upon coupling to a DOTA chelator. Two novel somatostatin analogs, 406-040-15 and its DOTA-coupled counterpart 406-051-20, with and without cold Indium labeling, were tested for their somatostatin receptor subtypes 1-5 (sst1-sst5) binding affinity using receptor autoradiography. Moreover, they were tested functionally for their ability to affect sst2 and sst3 internalization in vitro in HEK293 cells stably expressing the human sst2 or sst3 receptor, using an immunofluorescence microscopy-based internalization assay. All three compounds were characterized as pan-somatostatin analogs having a high affinity for all five sst. In the sst2 internalization assay, all three compounds showed an identical behavior, namely, a weak agonistic effect complemented by a weak antagonistic effect, compatible with the behavior of a partial agonist. Conversely, in the sst3 internalization assay, 406-040-15 was a full antagonist whereas its DOTA-coupled counterpart, 406-051-20, with and without Indium labeling, switched to a full agonist. Adding the DOTA chelator to the somatostatin analog 406-040-15 triggers a switch at sst3 receptor from an antagonist to an agonist. This indicates that potential radioligands for tumor targeting should always be tested functionally before further development, in particular if a chelator is added. (orig.)

  10. Analysis of the isomer ratios of polymethylated-DOTA complexes and the implications on protein structural studies.

    Science.gov (United States)

    Opina, Ana Christina L; Strickland, Madeleine; Lee, Yong-Sok; Tjandra, Nico; Andrew Byrd, R; Swenson, Rolf E; Vasalatiy, Olga

    2016-03-21

    A rigidified and symmetrical polymethylated 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) ligand bearing four SSSS methyl groups in both the tetraaza ring and the acetate arms (SSSS-SSSS-M4DOTMA) was prepared. The isomer ratio of SSSS-SSSS-M4DOTMA complexed with a series of lanthanide ions was carefully investigated using RP-HPLC and NMR. A square antiprismatic (SAP) configuration was exclusively observed for the early lanthanides, while the twisted square antiprismatic (TSAP) geometry was preferred as the lanthanide ion size decreases. The late lanthanides preferentially adopted the TSAP geometry. One of the pendant arms was modified with a pyridyl disulfide group (SSSS-SSSS-M8SPy) for cysteine attachment and displayed a similar isomer trend as the parent compound, Ln-SSSS-SSSS-M4DOTMA. Covalent attachment to the ubiquitin S57C mutant showed resonances whose intensities are in agreement with the isomeric population observed by RP-HPLC. Furthermore, the NOE experiments combined with quantum chemical calculations have unequivocally demonstrated that the SAP of Pr-SSSS-SSSS-M4DOTMA and Pr-SSSS-SSSS-M8SPy, as well as the TSAP of Yb-SSSS-SSSS-M8SPy are more stable than their corresponding isomers. PMID:26857249

  11. Novel approach for labeling of biopolymers with DOTA complexes using in situ click chemistry for quantification.

    Science.gov (United States)

    He, Yide; Esteban-Fernández, Diego; Linscheid, Michael W

    2015-03-01

    In this work, we present a two-step labeling approach for the efficient tagging with lanthanide-containing complexes. For this purpose, derivatization of the cysteine residues with an alkyne group acting as linker was done before the DOTA complex was introduced using in situ click chemistry. The characterization of this new methodology is presented including the optimization of the labeling process, demonstration of the quantitative capabilities using both electrospray ionization mass spectrometry (ESI-MS) and inductively coupled plasma mass spectrometry (ICP-MS) detection, and study of the fragmentation behavior of the labeled peptides by collision-induced dissociation (CID) for identification purposes. The results show that, in terms of labeling efficiency, this new methodology improves previously developed DOTA-based label strategies, such as MeCAT-maleimide (metal-coded affinity tag, MeCAT-Mal) and MeCAT-iodoacetamide (MeCAT-IA) reagents. The goal of reducing the steric hindrance caused by the voluminous DOTA complex was fulfilled allowing both, quantification and identification of labeled biopolymers.

  12. Structural Investigation for Optimization of Anthranilic Acid Derivatives as Partial FXR Agonists by in Silico Approaches

    Directory of Open Access Journals (Sweden)

    Meimei Chen

    2016-04-01

    Full Text Available In this paper, a three level in silico approach was applied to investigate some important structural and physicochemical aspects of a series of anthranilic acid derivatives (AAD newly identified as potent partial farnesoid X receptor (FXR agonists. Initially, both two and three-dimensional quantitative structure activity relationship (2D- and 3D-QSAR studies were performed based on such AAD by a stepwise technology combined with multiple linear regression and comparative molecular field analysis. The obtained 2D-QSAR model gave a high predictive ability (R2train = 0.935, R2test = 0.902, Q2LOO = 0.899. It also uncovered that number of rotatable single bonds (b_rotN, relative negative partial charges (RPC−, oprea's lead-like (opr_leadlike, subdivided van der Waal’s surface area (SlogP_VSA2 and accessible surface area (ASA were important features in defining activity. Additionally, the derived3D-QSAR model presented a higher predictive ability (R2train = 0.944, R2test = 0.892, Q2LOO = 0.802. Meanwhile, the derived contour maps from the 3D-QSAR model revealed the significant structural features (steric and electronic effects required for improving FXR agonist activity. Finally, nine newly designed AAD with higher predicted EC50 values than the known template compound were docked into the FXR active site. The excellent molecular binding patterns of these molecules also suggested that they can be robust and potent partial FXR agonists in agreement with the QSAR results. Overall, these derived models may help to identify and design novel AAD with better FXR agonist activity.

  13. Structural Investigation for Optimization of Anthranilic Acid Derivatives as Partial FXR Agonists by in Silico Approaches.

    Science.gov (United States)

    Chen, Meimei; Yang, Xuemei; Lai, Xinmei; Kang, Jie; Gan, Huijuan; Gao, Yuxing

    2016-01-01

    In this paper, a three level in silico approach was applied to investigate some important structural and physicochemical aspects of a series of anthranilic acid derivatives (AAD) newly identified as potent partial farnesoid X receptor (FXR) agonists. Initially, both two and three-dimensional quantitative structure activity relationship (2D- and 3D-QSAR) studies were performed based on such AAD by a stepwise technology combined with multiple linear regression and comparative molecular field analysis. The obtained 2D-QSAR model gave a high predictive ability (R²train = 0.935, R²test = 0.902, Q²LOO = 0.899). It also uncovered that number of rotatable single bonds (b_rotN), relative negative partial charges (RPC(-)), oprea's lead-like (opr_leadlike), subdivided van der Waal's surface area (SlogP_VSA2) and accessible surface area (ASA) were important features in defining activity. Additionally, the derived3D-QSAR model presented a higher predictive ability (R²train = 0.944, R²test = 0.892, Q²LOO = 0.802). Meanwhile, the derived contour maps from the 3D-QSAR model revealed the significant structural features (steric and electronic effects) required for improving FXR agonist activity. Finally, nine newly designed AAD with higher predicted EC50 values than the known template compound were docked into the FXR active site. The excellent molecular binding patterns of these molecules also suggested that they can be robust and potent partial FXR agonists in agreement with the QSAR results. Overall, these derived models may help to identify and design novel AAD with better FXR agonist activity. PMID:27070594

  14. Comparing organic acids and salt derivatives as antimicrobials against selected poultry-borne Listeria monocytogenes strains in vitro.

    Science.gov (United States)

    Lues, Jan Frederick Rykers; Theron, Maria Magdalena

    2012-12-01

    This article reports on the antilisterial properties of selected organic acids and salt derivatives in order to suggest possible alternatives in food preservation and pathogen control in the poultry meat processing industry. The susceptibility of two Listeria monocytogenes isolates was assessed against five organic acids (lactic, acetic, malic, citric, and propionic) and two acid-salt derivatives (sorbic acid [potassium salt] and benzoic acid [sodium salt]) across a series of pH environments. Minimum inhibitory concentrations (MICs) of the acids were tested against the two strains by means of an agar-dilution method. In general, strain CC60 was found to be more resistant than strain CC77 to both organic acids and salts. At pH values of 7 and above, high MIC levels (low susceptibility) were noted for potassium sorbate, sodium benzoate, and lactic acids, whereas susceptibility at lower pH increased reaching pH5 where the isolates were susceptible to all the organic acids tested. A small increase in pH notably reduced antimicrobial activity against the organisms. At pH 7, the isolates just about lost susceptibility to benzoic, lactic, malic, and sorbic acids. Although the activity of the majority of acids was linked to pH, some acids were not as closely related (e.g., potassium sorbate, sodium benzoate, and citric acid), and this suggests that the type of organic acids plays a role in inhibition. The relatively high MICs reported for compounds that are conventionally used as preservatives against Listeria spp. raise concern. The results furthermore suggest that the type of organic acid used to set pH, and not only pH alone, plays a role in determining inhibition. It was confirmed that a "one size fits all" approach to preservation is not always effective. Furthermore, the need for microbiological data to the subspecies level to inform the selection of preservatives was highlighted. PMID:23190165

  15. Radioiodinated phenylalkyl malonic acid derivatives as pH-sensitive SPECT tracers.

    Directory of Open Access Journals (Sweden)

    Matthias Bauwens

    Full Text Available INTRODUCTION: In vivo pH imaging has been a field of interest for molecular imaging for many years. This is especially important for determining tumor acidity, an important driving force of tumor invasion and metastasis formation, but also in the process of apoptosis. METHODS: 2-(4-[(123I]iodophenethyl-2-methylmalonic acid (IPMM, 2-(4-[(123I]iodophenethyl-malonic acid (IPM, 2-(4-[(123I]iodobenzyl-malonic acid (IBMM and 4-[(123I]iodophthalic acid (IP were radiolabeled via the Cu(+ isotopic nucleophilic exchange method. All tracers were tested in vitro in buffer systems to assess pH driven cell uptake. In vivo biodistribution of [(123I]IPMM and [(123I]IPM was determined in healthy mice and the pH targeting efficacy in vivo of [(123I]IPM was evaluated in an anti-Fas monoclonal antibody (mAb apoptosis model. In addition a mouse RIF-1 tumor model was explored in which tumor pH was decreased from 7.0 to 6.5 by means of induction of hyperglycemia in combination with administration of meta-iodobenzylguanidine. RESULTS: Radiosynthesis resulted in 15-20% for iodo-bromo exchange and 50-60% yield for iodo-iodo exchange while in vitro experiments showed a pH-sensitive uptake for all tracers. Shelf-life stability and in vivo stability was excellent for all tracers. [(123I]IPMM and [(123I]IPM showed a moderately fast predominantly biliary clearance while a high retention was observed in blood. The biodistribution profile of [(123I]IPM was found to be most favorable in view of pH-specific imaging. [(123I]IPM showed a clear pH-related uptake pattern in the RIF-1 tumor model. CONCLUSION: Iodine-123 labeled malonic acid derivates such as [(123I]IPM show a clearly pH dependent uptake in tumor cells both in vitro and in vivo which allows to visualize regional acidosis. However, these compounds are not suitable for detection of apoptosis due to a poor acidosis effect.

  16. Pharmacokinetics of chimeric L6 conjugated to indium-111- and yttrium-90-DOTA-peptide in tumor-bearing mice

    International Nuclear Information System (INIS)

    A bifunctional chelating agent, DOTA-Gly3-L-(p-isothiocyanato)-phenylalanine amide (DOTA-peptide-NCS), was studied in nude mice bearing human breast cancer xenografts (HBT 3477) to determine its potential for radioimmunoconjugate therapy. Indium-111 and yttrium-90 were attached to an anti-adenocarcinoma chimeric L6 (ChL6) monoclonal antibody (MAb) after pre-chelation to the DOTA-peptide-NCS and the desired neutral radiochelates were obtained by purification. The unique characteristic of the DOTA-peptide-NCS to form neutral complexes with trivalent metals was utilized to separate the resulting 111In and 90Y radiochelates from excess chelating agent and other anionic by-products resulting from metal impurities. The purified radiochelates were then conjugated to ChL6. The paramacokinetics of 111In- and 90Y-DOTA-peptide-ChL6 were obtained for 5 days after injection in nude mice bearing HBT 3477 xenographs. The results were compared with the pharmacokinetics of 125I-ChL6 obtained in the same mouse model. The whole-body clearance of 125I-ChL6, 90Y-and 111In-DOTA-peptide-ChL6 was monoexponential with biologic half-times of 92, 104 and 160 hr, respectively. Blood clearances of the three radiopharmaceuticals were biphasic. The radiometal immunoconjugates had greater tumor uptake and slower clearances. Indium-111- and 90Y-DOTA-peptide-ChL6 can be produced at high specific activity with fewer than one chelate per MAb by using a pre-labeling method that permits radiochelate purification by charge selection. Studies in mouse xenografts indicate that tumor uptake in enhanced and a favorable therapeutic index is achieved using these agents. 29 refs., 7 figs., 2 tabs

  17. Radiolabeling of DOTA-like conjugated peptides with generator-produced (68)Ga and using NaCl-based cationic elution method.

    Science.gov (United States)

    Mueller, Dirk; Breeman, Wouter A P; Klette, Ingo; Gottschaldt, Michael; Odparlik, Andreas; Baehre, Manfred; Tworowska, Izabela; Schultz, Michael K

    2016-06-01

    Gallium-68 ((68)Ga) is a generator-produced radionuclide with a short half-life (t½ = 68 min) that is particularly well suited for molecular imaging by positron emission tomography (PET). Methods have been developed to synthesize (68)Ga-labeled imaging agents possessing certain drawbacks, such as longer synthesis time because of a required final purification step, the use of organic solvents or concentrated hydrochloric acid (HCl). In our manuscript, we provide a detailed protocol for the use of an advantageous sodium chloride (NaCl)-based method for radiolabeling of chelator-modified peptides for molecular imaging. By working in a lead-shielded hot-cell system,(68)Ga(3+) of the generator eluate is trapped on a cation exchanger cartridge (100 mg, ∼8 mm long and 5 mm diameter) and then eluted with acidified 5 M NaCl solution directly into a sodium acetate-buffered solution containing a DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) or DOTA-like chelator-modified peptide. The main advantages of this procedure are the high efficiency and the absence of organic solvents. It can be applied to a variety of peptides, which are stable in 1 M NaCl solution at a pH value of 3-4 during reaction. After labeling, neutralization, sterile filtration and quality control (instant thin-layer chromatography (iTLC), HPLC and pH), the radiopharmaceutical can be directly administered to patients, without determination of organic solvents, which reduces the overall synthesis-to-release time. This procedure has been adapted easily to automated synthesis modules, which leads to a rapid preparation of (68)Ga radiopharmaceuticals (12-16 min). PMID:27172166

  18. Lewis Acid Pairs for the Activation of Biomass-derived Oxygenates in Aqueous Media

    Energy Technology Data Exchange (ETDEWEB)

    Roman, Yuriy [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

    2015-09-14

    The objective of this project is to understand the mechanistic aspects behind the cooperative activation of oxygenates by catalytic pairs in aqueous media. Specifically, we will investigate how the reactivity of a solid Lewis acid can be modulated by pairing the active site with other catalytic sites at the molecular level, with the ultimate goal of enhancing activation of targeted functional groups. Although unusual catalytic properties have been attributed to the cooperative effects promoted by such catalytic pairs, virtually no studies exist detailing the use heterogeneous water-tolerant Lewis pairs. A main goal of this work is to devise rational pathways for the synthesis of porous heterogeneous catalysts featuring isolated Lewis pairs that are active in the transformation of biomass-derived oxygenates in the presence of bulk water. Achieving this technical goal will require closely linking advanced synthesis techniques; detailed kinetic and mechanistic investigations; strict thermodynamic arguments; and comprehensive characterization studies of both materials and reaction intermediates. For the last performance period (2014-2015), two technical aims were pursued: 1) C-C coupling using Lewis acid and base pairs in Lewis acidic zeolites. Tin-, zirconium-, and hafnium containing zeolites (e.g., Sn-, Zr-, and Hf-Beta) are versatile solid Lewis acids that selectively activate carbonyl functional groups. In this aim, we demonstrate that these zeolites catalyze the cross-aldol condensation of aromatic aldehydes with acetone under mild reaction conditions with near quantitative yields. NMR studies with isotopically labeled molecules confirm that acid-base pairs in the Si-O-M framework ensemble promote soft enolization through α-proton abstraction. The Lewis acidic zeolites maintain activity in the presence of water and, unlike traditional base catalysts, in acidic solutions. 2) One-pot synthesis of MWW zeolite nanosheets for activation of bulky substrates. Through

  19. Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?

    Energy Technology Data Exchange (ETDEWEB)

    Antunes, P.; Ginj, M.; Zhang, H.; Maecke, H. [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); Waser, B.; Reubi, J.C. [University of Bern, Institute of Pathology, Bern (Switzerland); Baum, R.P. [Zentralklinik Bad Berka, Department of Nuclear Medicine/PETCT-Center, Bad Berka (Germany)

    2007-07-15

    Gallium-68 is a metallic positron emitter with a half-life of 68 min that is ideal for the in vivo use of small molecules, such as [{sup 68}Ga-DOTA,Tyr{sup 3}]octreotide, in the diagnostic imaging of somatostatin receptor-positive tumours. In preclinical studies it has shown a striking superiority over its {sup 111}In-labelled congener. The purpose of this study was to evaluate whether third-generation somatostatin-based, radiogallium-labelled peptides show the same superiority. Peptides were synthesised on solid phase. The receptor affinity was determined by in vitro receptor autoradiography. The internalisation rate was studied in AR4-2J and hsst-HEK-transfected cell lines. The pharmacokinetics was studied in a rat xenograft tumour model, AR4-2J. All peptides showed high affinities on hsst2, with the highest affinity for the Ga{sup III}-complexed peptides. On hsst3 the situation was reversed, with a trend towards lower affinity of the Ga{sup III} peptides. A significantly increased internalisation rate was found in sst2-expressing cells for all {sup 67}Ga-labelled peptides. Internalisation into HEK-sst3 was usually faster for the {sup 111}In-labelled peptides. No internalisation was found into sst5. Biodistribution studies employing [{sup 67}Ga-DOTA,1-Nal{sup 3}]octreotide in comparison to [{sup 111}In-DOTA,1-Nal{sup 3}]octreotide and [{sup 67}Ga-DOTA,Tyr{sup 3}]octreotide showed a significantly higher and receptor-mediated uptake of the two{sup 67}Ga-labelled peptides in the tumour and somatostatin receptor-positive tissues. A patient study illustrated the potential advantage of a broad receptor subtype profile radiopeptide over a high-affinity sst2-selective radiopeptide. This study demonstrates that {sup 67/68}Ga-DOTA-octapeptides show distinctly better preclinical, pharmacological performances than the {sup 111}In-labelled peptides, especially on sst2-expressing cells and the corresponding animal models. They may be excellent candidates for further

  20. Radiolabeling of NOTA and DOTA with Positron Emitting 68Ga and Investigation of In Vitro Properties

    International Nuclear Information System (INIS)

    We established radiolabeling conditions of NOTA and DOTA with a generator-produced PET radionuclide 68Ga and studied in vitro characteristics such as stability, serum protein binding, octanol/water distribution, and interference with other metal ions. Various concentrations of NOTA·3HCl and DOTA·4HCl were labeled with 1 mL 68GaCl3 (0.18∼5.75 mCi in 0.1 M HCl) in various pH. NOTA·3HCl (0.373 mM) was labeled with 68GaCl3 (0.183∼0.232 mCi/0.1 M HCl 1.0 mL) in the presence of CuCl2, FeCl2, InCl3, FeCl3, GaCl3, MgCl2 or CaCl2 (0∼6.07 mM) at room temperature. The labeling efficiencies of 68Ga-NOTA and 68Ga-DOTA were checked by ITLC-SG using acetone or saline as mobile phase. Stabilities, protein bindings, and octanol distribution coefficients of the labeled compounds also were investigated. 68Ga-NOTA and 68Ga-DOTA were labeled optimally at pH 6.5 and pH 3.5, respectively, and the chelates were stable for 4 hr either in the reaction mixture at room temperature or in the human serum at 37 .deg. C. NOTA was labeled at room temperature while DOTA required heating for labeling. 68Ga-NOTA labeling efficiency was reduced by CuCl2, FeCl2, InCl2, FeCl3 or GaCl3, however, was not influenced by MgCl2 or CaCl2. The protein binding was low (2.04∼3.32%). Log P value of 68Ga-NOTA was -3.07 indicating high hydrophilicity. We found that NOTA is a better bifunctional chelating agent than DOTA for 68Ga labeling. Although, 68Ga-NOTA labeling is interfered by various metal ions, it shows high stability and low serum protein binding

  1. Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?

    International Nuclear Information System (INIS)

    Gallium-68 is a metallic positron emitter with a half-life of 68 min that is ideal for the in vivo use of small molecules, such as [68Ga-DOTA,Tyr3]octreotide, in the diagnostic imaging of somatostatin receptor-positive tumours. In preclinical studies it has shown a striking superiority over its 111In-labelled congener. The purpose of this study was to evaluate whether third-generation somatostatin-based, radiogallium-labelled peptides show the same superiority. Peptides were synthesised on solid phase. The receptor affinity was determined by in vitro receptor autoradiography. The internalisation rate was studied in AR4-2J and hsst-HEK-transfected cell lines. The pharmacokinetics was studied in a rat xenograft tumour model, AR4-2J. All peptides showed high affinities on hsst2, with the highest affinity for the GaIII-complexed peptides. On hsst3 the situation was reversed, with a trend towards lower affinity of the GaIII peptides. A significantly increased internalisation rate was found in sst2-expressing cells for all 67Ga-labelled peptides. Internalisation into HEK-sst3 was usually faster for the 111In-labelled peptides. No internalisation was found into sst5. Biodistribution studies employing [67Ga-DOTA,1-Nal3]octreotide in comparison to [111In-DOTA,1-Nal3]octreotide and [67Ga-DOTA,Tyr3]octreotide showed a significantly higher and receptor-mediated uptake of the two67Ga-labelled peptides in the tumour and somatostatin receptor-positive tissues. A patient study illustrated the potential advantage of a broad receptor subtype profile radiopeptide over a high-affinity sst2-selective radiopeptide. This study demonstrates that 67/68Ga-DOTA-octapeptides show distinctly better preclinical, pharmacological performances than the 111In-labelled peptides, especially on sst2-expressing cells and the corresponding animal models. They may be excellent candidates for further development for clinical studies. (orig.)

  2. Poly-Acrylic Acid Derivatives as Diesel Flow Improver for Paraffin-Based Daqing Diesel

    Institute of Scientific and Technical Information of China (English)

    Cuiyu Jiang; Ming Xu; Xiaoli Xi; Panlun Qi; Hongyan Shang

    2006-01-01

    Since the diesel products from paraffin-based Daqing crude oil showed low sensitivity to certain commercial diesel pour point depressant (PPDs) that resulted from the high content of paraffin, certain poly-acrylic acid derivatives (PADE) with-COOR,-COOH,-CONHR, and -COO-NH3+R groups by molecular design on the mechanics of diesel; PPDs were synthesized and evaluated as cold flow improver for Daqing 0# diesel in this paper. The pure PADE was superior to the commercial PPDs and displayed a substantial ability of wax crystals dispersion. There was a synergistic effect among the PADE and T1804 and secondary amine. The synergism clearly improved the low temperature performance of Daqing diesel products and could reduce the cold filter plugging point of 0# diesel by 6-7 ℃.

  3. Fluorinated betulinic acid derivatives and evaluation of their anti-HIV activity.

    Science.gov (United States)

    Li, Jizhen; Goto, Masuo; Yang, Xiaoming; Morris-Natschke, Susan L; Huang, Li; Chen, Chin-Ho; Lee, Kuo-Hsiung

    2016-01-01

    Several fluorinated derivatives of the anti-HIV maturation agent bevirimat (1) were synthesized and evaluated for anti-HIV replication activity. The modified positions were the C-2, C-3, C-28, and C-30 positions, either directly on the betulinic acid (2) skeleton or in the attached side chains. Compound 18, which has a trifluoromethyl group added to C-30 of its isopropenyl group, exhibited similar potency to 1 against HIV-1NL4-3. In total, our current studies support our prior conclusion that C-30 allylic modification is unlikely to be a pharmacophore for anti-HIV activity, but could be a meaningful route to manipulate other properties of 2-related compounds.

  4. Bioactive Compounds Derived from the Yeast Metabolism of Aromatic Amino Acids during Alcoholic Fermentation

    Directory of Open Access Journals (Sweden)

    Albert Mas

    2014-01-01

    Full Text Available Metabolites resulting from nitrogen metabolism in yeast are currently found in some fermented beverages such as wine and beer. Their study has recently attracted the attention of researchers. Some metabolites derived from aromatic amino acids are bioactive compounds that can behave as hormones or even mimic their role in humans and may also act as regulators in yeast. Although the metabolic pathways for their formation are well known, the physiological significance is still far from being understood. The understanding of this relevance will be a key element in managing the production of these compounds under controlled conditions, to offer fermented food with specific enrichment in these compounds or even to use the yeast as nutritional complements.

  5. Sesquiterpenes, flavonoids, shikimic acid derivatives and pyrrolizidine alkaloids from Senecio kingii Hook.

    Science.gov (United States)

    Ruiz-Vásquez, Liliana; Reina, Matías; López-Rodríguez, M; Giménez, Cristina; Cabrera, Raimundo; Cuadra, Pedro; Fajardo, Víctor; González-Coloma, Azucena

    2015-09-01

    Twenty-four compounds including eleven eremophilanolides (1-11), one eremophilane (13), five shikimic acid derivatives (14-18), six flavonoids (19-24), and the macrocyclic unsaturated pyrrolizidine alkaloid integerrimine (25) were isolated from Senecio kingii, an endemic species from the Magallanes Region (Chile). Compounds 3, 5, 6, 8-11 and 13-18 have not been previously reported as natural products. Their molecular structures were determined by NMR spectroscopic analysis and comparison with published NMR data. An X-ray-analysis of compound 3 has been performed. Their insecticidal and antifungal activities were tested, being compound 3 the strongest insect antifeedant. Compounds 6, 9 and 18 were moderate antifungals. PMID:26101146

  6. Synthesis of some novel D-glucuronic acid acetylated derivatives as potential anti-tumor agents.

    Science.gov (United States)

    El-Nezhawy, Ahmed O H; Adly, Frady G; Eweas, Ahmed F; Hanna, Atef G; El-Kholy, Yehya M; El-Sayed, Shahenaz H; El-Naggar, Tarek B A

    2011-10-01

    A structurally diverse series of Δ(4,5) -uronamide derivatives have been chemically synthesized starting from D-glucuronic acid itself by means of acetylation, activation, amide bond formation and base-catalyzed elimination protocols. Structure elucidation for all products along with optimization of the synthetic steps is described. The synthesized compounds were evaluated for their in-vitro anti-tumor activity against MCF-7, TK-10 and UACC-62 cell lines. The compounds 5, 11, 13, 15 and 16 were the most active against TK-10 cell line. On the other hand, the most active compounds against the MCF-7 cell line were 11 and 15. However, compounds 5, 7, 11, 13, 15 and 16 were the most active against the UACC-62 cell line.

  7. Bioactive Compounds Derived from the Yeast Metabolism of Aromatic Amino Acids during Alcoholic Fermentation

    Science.gov (United States)

    Guillamon, Jose Manuel; Torija, Maria Jesus; Beltran, Gemma; Troncoso, Ana M.; Garcia-Parrilla, M. Carmen

    2014-01-01

    Metabolites resulting from nitrogen metabolism in yeast are currently found in some fermented beverages such as wine and beer. Their study has recently attracted the attention of researchers. Some metabolites derived from aromatic amino acids are bioactive compounds that can behave as hormones or even mimic their role in humans and may also act as regulators in yeast. Although the metabolic pathways for their formation are well known, the physiological significance is still far from being understood. The understanding of this relevance will be a key element in managing the production of these compounds under controlled conditions, to offer fermented food with specific enrichment in these compounds or even to use the yeast as nutritional complements. PMID:24895623

  8. STRUCTURE BASED DRUG DESIGN STUDIES ON HETEROARYL PROPANOIC ACID DERIVATIVES AS PPARΓ AGONISTS

    Directory of Open Access Journals (Sweden)

    ARUN KUMAR,MANGA RATNAM,ARCHANA KUMARI, AJAY BABU

    2013-09-01

    Full Text Available Peroxisome proliferator-activated receptors (PPARs are a group of nuclear receptorproteins. Docking studies are based on several factors. Among 15 entries of PPARγ, 2Q6S wastaken for docking analysis, as it showed 418 most favored regions, 35 in additionally allowedregion and none of the residue in disallowed regions. To carry out drug designing, moleculeswere considered from the literature in which substitution of R1 position with dihydrofurylreported to have high dock score (-14.98 Kcal/mol than the remaining analogues, with bettergeometry and interactions. Hence docking analysis using heteroaryl propionic acid derivatives asanti-diabetic agents suggest the reproducibility of active molecules being predicted bycomputational docking studies using Auto dock software.

  9. INFLUENCE OF AROMATIC AMINO ACID DERIVATIVES ON THE LEVELS OF IMMUNE COMPLEXES UNDER IONIZED RADIATION

    Directory of Open Access Journals (Sweden)

    A. S. Boyajyan

    2009-01-01

    Full Text Available Abstract. In the present study, blood levels of circulating immune complexes and of their pathogenic subpopulations were determined in rats following ionizing irradiation. Experimental animals were treated with synthetic Schiff base aromatic amino acid derivatives, nicotinyl-L-tyrosinate or nicotinyl-L-tryptophanate, before irradiation, whereas untreated irradiated rats served as controls. The results obtained demonstrate significantly increased levels of immune complexes, as well as presence of a pathogenic subpopulation of circulating immune complexes in blood of irradiated animals. In addition, the data obtained suggest a normalizing effect of nicotinyl-L-tyrosinate and nicotinyl-L-tryptophanate upon the mentioned parameters. On the basis of these observations, a cyto- and immunoprotective ability of nicotinyl-L-tyrosinate and nicotinyl-L-tryptophanate may be proposed.

  10. The local atomic structure of di-alanine amino acid derivative of protoporphyrin IX

    International Nuclear Information System (INIS)

    The photophysical and photochemical properties of photosensitizers bearing potential for photodynamic diagnosis (PDD) and treatment (PDT) of malignant tissues strictly depend on the details of their chemical processing. In this work, the x-ray absorption spectroscopy (XAFS) and electron spin resonance (ESR) techniques were applied to determine the nearest neighbourhood of iron in the di-alanine amino acid derivative of protoporphyrin IX (L-alanine diprotoporphyrinate). The investigated compound is a technological precursor for novel-class, highly water-soluble protoporphyrin IX-based photosensitizers, which have potential for applications in PDD and PDT and have just entered phase I clinical trials. Knowing the chemical content and exact atomic structures of the technological precursor, as well as of the high-purity final product, which all might contain some contamination, is a prerequisite for preparing photosensitizers for preliminary clinical tests

  11. Effect of 2-Hydroxypropyl-β-cyclodextrin on Solubility of Sparingly Soluble Drug Derivatives of Anthranilic Acid

    OpenAIRE

    Aneta Pobudkowska; Aleksandra Pelczarska; Urszula Domańska

    2011-01-01

    Guest-host complex formation of three drug derivatives of anthranilic acid, mefenamic acid, niflumic acid, and flufenamic acid with 2-hydroxypropyl-β-cyclodextrin (2HP-β-CD) in aqueous solutions was investigated using “Phase solubility study” with UV-vis spectrophotometry. Solubility of sparingly soluble drugs has been improved by addition of 2HP-β-CD at two temperatures 298.15 K and 310.15 K and two pH values 2 and 7. The influence of different 2HP-β-CD concentration on solubility of drugs a...

  12. New Polyamides Based on Bis(p-amidobenzoic acid)-p-phenylene diacrylic acid and Hydantoin Derivatives: Synthesis and Characterization

    OpenAIRE

    FAGHIHI, Khalil

    2008-01-01

    Bis(p-amidobenzoic acid)-p-phenylene diacrylic acid (6) as a new monomer containing p-phenylenediacryloyl moiety was synthesized by using a 3-step reaction. At first p-phenylenediacrylic acid (3) was prepared by reaction of terephthal aldehyde (1) with malonic acid (2) in the presence of pyridine, and then diacid 3 was converted to p-phenylenediacryloyl chloride (4) by reaction with thionyl chloride. Finally bis(p-amidobenzoic acid)-p-phenylene diacrylic acid (6) was prepared by the ...

  13. Synthesis and description of intermolecular interactions in new sulfonamide derivatives of tranexamic acid

    Science.gov (United States)

    Ashfaq, Muhammad; Arshad, Muhammad Nadeem; Danish, Muhammad; Asiri, Abdullah M.; Khatoon, Sadia; Mustafa, Ghulam; Zolotarev, Pavel N.; Butt, Rabia Ayub; Şahin, Onur

    2016-01-01

    Tranexamic acid (4-aminomethyl-cyclohexanecarboxylic acid) was reacted with sulfonyl chlorides to produce structurally related four sulfonamide derivatives using simple and environmental friendly method to check out their three-dimensional behavior and van der Walls interactions. The molecules were crystallized in different possibilities, as it is/after alkylation at its O and N atoms/along with a co-molecule. All molecules were crystallized in monoclinic crystal system with space group P21/n, P21/c and P21/a. X-ray studies reveal that the molecules stabilized themselves by different kinds of hydrogen bonding interactions. The molecules are getting connected through O-H⋯O hydrogen bonds to form inversion dimers which are further connected through N-H⋯O interactions. The molecules in which N and O atoms were alkylated showed non-classical interaction and generated centro-symmetric R22(24) ring motif. The co-crystallized host and guest molecules are connected to each other via O-H⋯O interactions to generate different ring motifs. By means of the ToposPro software an analysis of the topologies of underlying nets that correspond to molecular packings and hydrogen-bonded networks in structures under consideration was carried out.

  14. Usnic Acid Derivatives with Cytotoxic and Antifungal Activities from the Lichen Usnea longissima.

    Science.gov (United States)

    Yu, Xuelong; Guo, Qiang; Su, Guozhu; Yang, Ailin; Hu, Zhongdong; Qu, Changhai; Wan, Zhe; Li, Ruoyu; Tu, Pengfei; Chai, Xingyun

    2016-05-27

    Eight usnic acid derivatives, that is, usenamines A-F (1-6), usone (7), and isousone (8), together with the known (+)-usnic acid (9), were isolated from the lichen Usnea longissima. Their structures were elucidated using 1D and 2D NMR and MS data, and the absolute configurations of compounds 1 and 2 were defined by single-crystal X-ray diffraction analyses. Compounds 1, 2, and 8 showed inhibitory effects on the growth of human hepatoma HepG2 cells with IC50 values of 6.0-53.3 μM compared with methotrexate as the positive control, which had an IC50 value of 15.8 μM. Furthermore, 1 induced apoptosis of HepG2 cells in a dose-dependent manner at concentrations of 0-15.0 μM. The isolated compounds were also evaluated for their antifungal and antibacterial activities, with 7 and 8 exhibiting weak inhibitory effects on fungal Trichophyton rubrum spp. with an MIC value of 41.0 μM. PMID:27186821

  15. Synthesis, structural characterization and quantum chemical studies of silicon-containing benzoic acid derivatives

    Science.gov (United States)

    Zaltariov, Mirela-Fernanda; Cojocaru, Corneliu; Shova, Sergiu; Sacarescu, Liviu; Cazacu, Maria

    2016-09-01

    The present paper is concerned with the synthesis and molecular structure investigation of two new benzoic acid derivatives having trimethylsilyl tails, 4-((trimethylsilyl)methoxy) and 4-(3-(trimethylsilyl)propoxy)benzoic acids. The structures of the novel compounds have been confirmed by X-ray crystallography, Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (1H and 13C NMR). The theoretical studies of molecules were conducted by using the quantum chemical methods, such as Density Functional Theory (DFT B3LYP/6-31 + G**), Hartree-Fock (HF/6-31 + G**) and semiempirical computations (PM3, PM6 and PM7). The optimized molecular geometries have been found to be in good agreement with experimental structures resulted from the X-ray diffraction. The maximum electronic absorption bands observed at 272-287 nm (UV-vis spectra) have been assigned to π → π* transitions, which were in reasonable agreement with the time dependent density functional theory (TD-DFT) calculations. The computed vibrational frequencies by DFT method were assigned and compared with the experimental FTIR spectra. The mapped electrostatic potentials revealed the reactive sites, which corroborated the observation of the dimer supramolecular structures formed in the crystals by hydrogen-bonding. The energies of frontier molecular orbitals (HOMO and LUMO), energy gap, dipole moment and molecular descriptors for the new compounds were calculated and discussed.

  16. Effect of Retinoic acid on Platelet-derived Growth Factor and Lung Development in Newborn Rats

    Institute of Scientific and Technical Information of China (English)

    陈红兵; 常立文; 刘汉楚; 容志惠; 祝华平; 张谦慎; 李文斌

    2004-01-01

    Summary: The influence of platelet-derived growth factor (PDGF) on lung development in newborn rats and the effect of retinoic acid (RA) on PDGF in lung development were investigated. Newborn Sprague-Dawley (SD) rats were randomly assigned to two groups: control group and RA group.The rats in RA group was intraperitoneally injected with all trans-retinoic acid (500 μg/kg every day) for consecutive 3 days after birth, while those in the control group were not subjected to intervention, Immunohistochemical assay was performed to locate the expression of PDGF. mRNA levels of PDGF were measured by reverse transcription polymerase chain reaction (RT-PCR) at age of 1, 3, 5, 7, 10, 14, 21 days. The method of radial alveolar counts (RAC) was used to measure the amount of the alveoli of the lungs. It was found that with increasing days, levels of PDGF-A and PDGF-B changed to verying degrees. RA could elevate significantly the expression levels of PDGF A mRNA and protein (P<0.01), but not affect the expression levels of PDGF-B mRNA and pro tein markedly (P>0.05). It is suggested that PDGF might play an important role in lung development. RA can stimulate lung development through increasing the expression levels of PDGF-A mRNA and protein.

  17. Antitrypanosomal Acetylene Fatty Acid Derivatives from the Seeds of Porcelia macrocarpa (Annonaceae).

    Science.gov (United States)

    de Á Santos, Luciana; Cavalheiro, Alberto J; Tempone, Andre G; Correa, Daniela S; Alexandre, Tatiana R; Quintiliano, Natalia F; Rodrigues-Oliveira, André F; Oliveira-Silva, Diogo; Martins, Roberto Carlos C; Lago, João Henrique G

    2015-05-07

    Chagas' disease is caused by a parasitic protozoan and affects the poorest population in the world, causing high mortality and morbidity. As a result of the toxicity and long duration of current treatments, the discovery of novel and more efficacious drugs is crucial. In this work, the hexane extract from seeds of Porcelia macrocarpa R.E. Fries (Annonaceae) displayed in vitro antitrypanosomal activity against trypomastigote forms of T. cruzi by the colorimetric MTT assay (IC50 of 65.44 μg/mL). Using chromatographic fractionation over SiO2, this extract afforded a fraction composed by one active compound (IC50 of 10.70 µg/mL), which was chemically characterized as 12,14-octadecadiynoic acid (macrocarpic acid). Additionally, two new inactive acetylene compounds (α,α'-dimacro-carpoyl-β-oleylglycerol and α-macrocarpoyl-α'-oleylglycerol) were also isolated from the hexane extract. The complete characterization of the isolated compounds was performed by analysis of NMR and MS data as well as preparation of derivatives.

  18. Antitrypanosomal Acetylene Fatty Acid Derivatives from the Seeds of Porcelia macrocarpa (Annonaceae

    Directory of Open Access Journals (Sweden)

    Luciana de Á. Santos

    2015-05-01

    Full Text Available Chagas’ disease is caused by a parasitic protozoan and affects the poorest population in the world, causing high mortality and morbidity. As a result of the toxicity and long duration of current treatments, the discovery of novel and more efficacious drugs is crucial. In this work, the hexane extract from seeds of Porcelia macrocarpa R.E. Fries (Annonaceae displayed in vitro antitrypanosomal activity against trypomastigote forms of T. cruzi by the colorimetric MTT assay (IC50 of 65.44 μg/mL. Using chromatographic fractionation over SiO2, this extract afforded a fraction composed by one active compound (IC50 of 10.70 µg/mL, which was chemically characterized as 12,14-octadecadiynoic acid (macrocarpic acid. Additionally, two new inactive acetylene compounds (α,α'-dimacro-carpoyl-β-oleylglycerol and α-macrocarpoyl-α'-oleylglycerol were also isolated from the hexane extract. The complete characterization of the isolated compounds was performed by analysis of NMR and MS data as well as preparation of derivatives.

  19. Sorption of a triazol derivative by soils: importance of surface acidity

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The sorption of a triazol derivative, 1-(4-chlorophenyl)- 4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl)penten-3-ol with a common name of S3307D, on fifteen soils and three H2O2-treated soils was investigated. The sorption isotherm for each untreated and treated soil was non-linear, and was best fitted to Freundlich sorption equation. Soils containing high amount of clay content or organic matter or both sorbed much higher amounts of the chemical than soils that had low contents of these soil constituents. H2O2-treated soils showed considerable sorptive affinity for S3307D. It was concluded that both organic matter and mineral fraction in natural soils contributed to the sorption of the basic compound. Sorption by the H2O2 treated soils increased as suspension pH decreased, but all suspension pHs exceeded the pKa of the compound by more than two units. This implies that organic base protonation can occur on surfaces of soil components, and surface acidity (exchangeable acidity ) is important in sorption process of the organic base rather than suspension pH.

  20. Biodegradation of novel amino acid derivatives suitable for complexing agents in pulp bleaching applications.

    Science.gov (United States)

    Metsärinne, Sirpa; Ronkainen, Erja; Tuhkanen, Tuula; Aksela, Reijo; Sillanpää, Mika

    2007-05-01

    The biodegradability of four novel diethanolamine derivative complexing agents was examined by using two biodegradation tests standardised by OECD (301B and 301F). Ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) were employed as reference substances. Biodegradation of the new complexing agents was studied both with unacclimated and acclimated inocula as well as by simulating wastewater treatment in sequencing batch reactors (SBRs). These new complexing agents were of technical grade, and therefore, the results are only indicative but these new compounds hold promise for use as complexing agents in the pulp and paper industry. The novel complexing agents were not readily biodegradable but they showed slight biodegradation. Around 10-30% degradation was found in the SBR where degradation was followed by measurement of concentration. Moreover the novel complexing agents did not have any negative impact on reactor performance as measured by chemical oxygen demand reduction. In the standardised biodegradation tests at best around 50% degradation was observed with the acclimated inoculum and in the prolonged test whereas EDTA and DTPA exhibited no biodegradation. The elevated degradation in acclimated sludge indicates that the water treatment plant microbes are capable of decomposing these molecules under favourable conditions. The total concentration of novel complexing agents decreased slightly during biodegradation tests, while the EDTA and DTPA concentrations remained stable. PMID:17346781