共查询到20条相似文献,搜索用时 15 毫秒
1.
S Gupta J K Srivastava M K Jain J C Katiyar J Singh D S Bhakuni 《Indian journal of experimental biology》1991,29(7):645-648
Methyl 5(6)-(alpha-hydroxyphenylmethyl) benzimidazole-2- carbamate, a metabolite of mebendazole, was evaluated against metamorphic forms of Ancylostoma ceylanicum in hamsters, Nippostrongylus brasiliensis in rats and cysticercoids of Hymenolepis nana in grain beetles. The test compound offered better action than mebendazole except against H. nana cysticercoids where the activity of the compound and mebendazole was comparable, but was inferior to the standard cestodicidal drug, praziquantel. The results suggest that the action was better by ip route compared to per os route of drug administration. 相似文献
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S Gupta A M Khan M K Jain J C Katiyar S S Naim S K Singh S Sharma 《Indian journal of experimental biology》1990,28(5):475-479
Biological evaluation of methyl 5(6)-(4-methylpiperidin-1-yl) carbonylbenzimidazole-2-carbamate against Ancylostoma ceylanicum, Nippostrongylus brasiliensis, Syphacia obvelata, Hymenolepis nana, H. diminuta and Cysticercus fasciolaris in experimental animals is reported. The compound (mg/kg) causes 100% elimination of A. ceylanicum (25 x 1), N. brasiliensis (100 x 1), S. obvelata (50 x 1), H. nana (250 x 3) and C. fasciolaris (50 x 10). It was also effective against the developing larvae (L3, L4 and L5) of A. ceylanicum at a single oral dose of 100 mg/kg. Another study indicated that the compound elicits 100% response within 32 hr of drug administration. The drug is well tolerated and LD50 is greater than 4500 mg/kg. 相似文献
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Rameshwar N Krishna K Ashok Kumar B Parthasarathy T 《Bioorganic & medicinal chemistry》2006,14(2):319-325
Factor X(a) has materialized as a key enzyme for the intervention of blood coagulation cascade and for the development of new antithrombotic agents. It is the lone enzyme that is responsible for the production of thrombin and is therefore an attractive target for the control of thrombus formation. The biological activities (log1/IC(50)) of anthranilamide-based factor X(a) inhibitors were quantitatively analyzed in terms of physicochemical parameters by the regression analysis. Structural requirements for maximal potency were derived from the results of a quantitative structure activity relationship analysis. The leave-one-out cross-validation method was used to judge the predictive power of final equations. 相似文献
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Synthesis of methyl 2- and 4-pyridyl disulfide from 2- and 4-thiopyridone and methyl methanethiosulfonate 总被引:1,自引:0,他引:1
In 1982, methyl 2-pyridyl disulfide was reported as a new reagent for the titration of thiol groups in peptides and proteins and for their temporary blocking with the thiomethyl group [T. Kimura et al. (1982) Anal. Biochem. 122, 274-282]. We have synthesized this compound (and its 4-pyridyl isomer) by a rapid and convenient procedure which is preferable to that in the original report. Our method involves the thiomethylation of the appropriate thiopyridone by methyl methanethiosulfonate. 相似文献
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J K Srivastava S Gupta J C Katiyar V M Srivastava 《Indian journal of experimental biology》1989,27(8):735-738
Effects of methyl [5[[4-(2-pyridinyl)-1-piperazinyl] carbonyl] 1H-benzimidazol-2-yl] carbamate (CDRI Comp. 81-470) and mebendazole on the energy metabolism of A. ceylanicum and N. brasiliensis were compared. At 10 and 50 microM concentration both compounds inhibited glucose uptake and its conversion into metabolic endproducts. The shift towards the increased production of lactic acid appeared to be the result of inhibition of PEP carboxykinase and increase in LDH activity. The compounds also caused significant inhibition of ATP production in mitochondria. 相似文献
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Kuchar M Hocek M Pohl R Votruba I Shih IH Mabery E Mackman R 《Bioorganic & medicinal chemistry》2008,16(3):1400-1424
An efficient and facile synthesis of a large series of diverse 6-[2-(dialkylamino)vinyl]-, 6-[2-(dialkylamino)ethyl]-, 6-(2-alkoxyethyl)-, and 6-[2-(alkylsulfanyl)ethyl]purine nucleosides (35 examples of both ribo- and 2'-deoxyribonucleosides) was developed. The key transformations involved conjugate nucleophilic additions of amines, alcoholates, or thiolates to Tol-protected 6-alkylylpurine or 6-vinylpurine nucleosides. 6-[(2-Dialkylamino)vinyl]- and some 6-[(2-dialkylamino)ethyl]purine ribonucleosides exerted significant cytostatic effects and some anti-HCV activity with low selectivity. 相似文献
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Masaki Setoguchi Shin Iimura Yuuichi Sugimoto Yoshiyuki Yoneda Jun Chiba Toshiyuki Watanabe Fumihito Muro Yutaka Iigo Gensuke Takayama Mika Yokoyama Tomoe Taira Misato Aonuma Tohru Takashi Atsushi Nakayama Nobuo Machinaga 《Bioorganic & medicinal chemistry》2013,21(1):42-61
We have carried out the optimization of substituents at the C-3 or the C-5 position on the pyrrolidine ring of VLA-4 antagonist 3 with 2-(phenylamino)-7-fluorobenzoxazolyl moiety for the purpose of improving in vivo efficacy while maintaining good aqueous solubility. As a result, we successfully increased in vitro activity in the presence of 3% human serum albumin and achieved an exquisite lipophilic and hydrophilic balance of compounds suitable for oral administrative regimen. The modification resulted in the identification of zwitterionic compound 7n with (5S)-[methoxy(methyl)amino]methylpyrrolidine, which significantly alleviated bronchial hyper-responsiveness to acetylcholine chloride at 12.5 mg/kg, p.o. in a murine asthma model and showed favorable aqueous solubility (JP1, 89 μg/mL; JP2, 462 μg/mL). Furthermore, this compound showed good oral bioavailability (F = 54%) in monkeys. 相似文献
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Maria Koufaki Theano Fotopoulou Efstathios K. Iliodromitis Sophia-Iris Bibli Anastasia Zoga Dimitrios Th. Kremastinos Ioanna Andreadou 《Bioorganic & medicinal chemistry》2012,20(19):5948-5956
Novel purine analogues bearing nitrate esters were designed and synthesized in an effort to develop compounds triggering endogenous cardioprotective mechanisms such as ischemic preconditioning (IPC) or postconditioning (PostC). The majority of the compounds reduced infarct size compared to the control group in anesthetized rabbits, whereas administration of the most active analogue 16 at a dose of 3.8 μmol/kg resulted on a significant reduction of infarct size, compared to PostC group (13.4 ± 1.9% vs 26.4 ± 2.3%). These findings introduce a novel class of promising pharmacological compounds that could be used as mimics or enhancers of PostC. 相似文献
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A synthesis of alpha-D-Manp-(1----3)-[beta-D-GlcpNAc-(1----4)]-[alpha-D-Manp++ +-(1----6)]- beta-D-Manp-(1----4)-beta-D-GlcpNAc-(1----4)-[alpha-L-Fucp-( 1----6)]-D- GlcpNAc was achieved by employing benzyl O-(3,4,6-tri-O-benzyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl)-(1--- -4)-O- (2-O-benzyl-beta-D-mannopyranosyl)-(1----4)-O-(3,6-di-O-benzyl-2-deoxy-2 - phthalimido-beta-D-glucopyranosyl)-(1----4)-3-O-benzyl-2-deoxy-6-O-p- methoxyphenyl-2-phthalimido-beta-D-glucopyranoside as a key glycosyl acceptor. Highly stereoselective mannosylation was performed by taking advantage of the 2-O-acetyl group in the mannosyl donors. The alpha-L-fucopyranosyl residue was also stereoselectively introduced by copper(II)-mediated activation of methyl 2,3,4-tri-O-benzyl-1-thio-beta-L-fucopyranoside. 相似文献
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We have previously shown that whereas (RS)-2-amino-3-(3-hydroxy-5-phenylisoxazol-4-yl)propionic acid (APPA) shows the characteristics of a partial agonist at (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors, (S)-APPA is a full AMPA receptor agonist and (R)-APPA a weak competitive AMPA receptor antagonist. This observation led us to introduce the new pharmacological concept, functional partial agonism. Recently we have shown that the 2-pyridyl analogue of APPA, (RS)-2-amino-3-[3-hydroxy-5-(2-pyridyl)isoxazol-4-yl]propionic acid (2-Py-AMPA), is a potent and apparently full AMPA receptor agonist, and this compound has now been resolved into (+)- and (-)-2-Py-AMPA (ee ≥ 99.0%) by chiral HPLC using a Chirobiotic T column. The absolute stereochemistry of the enantiomers of APPA has previously been established by X-ray analysis, and on the basis of comparative studies of the circular dichroism spectra of the enantiomers of APPA and 2-Py-AMPA, (+)- and (-)-2-Py-AMPA were assigned the (S)- and (R)-configuration, respectively. In a series of receptor binding studies, neither enantiomer of 2-Py-AMPA showed detectable affinity for kainic acid receptor sites or different sites at the N-methyl-D-aspartic acid (NMDA) receptor complex. (+)-(S)-2-Py-AMPA was an effective inhibitor of [3H]AMPA binding (IC50 = 0.19 ± 0.06 μM) and a potent AMPA receptor agonist in the rat cortical wedge preparation (EC50 = 4.5 ± 0.3 μM) comparable with AMPA (IC50 = 0.040 ± 0.01 μM; EC50 = 3.5 ± 0.2 μM), but much more potent than (+)-(S)-APPA (IC50 = 5.5 ± 2.2 μM; EC50 = 230 ± 12 μM). Like (-)-(R)-APPA (IC50 > 100 μM), (-)-(R)-2-Py-AMPA (IC50 > 100 μM) did not significantly affect [3H]AMPA binding, and both compounds were week AMPA receptor antagonists (Ki = 270 ± 50 and 290 ± 20 μM, respectively). Chirality 9:274–280, 1997. © 1997 Wiley-Liss, Inc. 相似文献
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F M Uckun C Mao S Pendergrass D Maher D Zhu L Tuel-Ahlgren T K Venkatachalam 《Bioorganic & medicinal chemistry letters》1999,9(18):2721-2726
We have replaced the pyridyl ring of trovirdine with an alicyclic cyclohexenyl, adamantyl or cis-myrtanyl ring. Only the cyclohexenyl-containing thiourea compound N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-bromopyridyl)]- thiourea (HI-346) (as well as its chlorine-substituted derivative N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-chloropyridyl)]- thiourea/HI-445) showed RT inhibitory activity. HI-346 and HI-445 effectively inhibited recombinant RT with better IC50 values than other anti-HIV agents tested. The ranking order of efficacy in cell-free RT inhibition assays was: HI-346 (IC50 = 0.4 microM) > HI-445 (IC50 = 0.5 microM) > trovirdine (IC50 = 0.8 microM) > MKC-442 (IC5 = 0.8 microM) = delavirdine (IC50 = 1.5 microM) > nevirapine (IC50 = 23 microM). In accord with this data, both compounds inhibited the replication of the drug-sensitive HIV-1 strain HTLV(IIIB) with better IC50 values than other anti-HIV agents tested. The ranking order of efficacy in cellular HIV-1 inhibition assays was: HI-445 = HI-346 (IC50 = 3 nM) > MKC-442 (IC50 = 4 nM) = AZT (IC50 = 4 nM) > trovirdine (IC50 = 7 nM) > delavirdine (IC50 = 9 nM) > nevirapine (IC50 = 34 nM). Surprisingly, the lead compounds HI-346 and HI-445 were 3-times more effective against the multidrug resistant HIV-1 strain RT-MDR with a V106A mutation (as well as additional mutations involving the RT residues 74V,41L, and 215Y) than they were against HTLV(IIIB) with wild-type RT. HI-346 and HI-445 were 20-times more potent than trovirdine, 200-times more potent than AZT, 300-times more potent than MKC-442, 400-times more potent than delavirdine, and 5000-times more potent than nevirapine against the multidrug resistant HIV-1 strain RT-MDR. HI-445 was also tested against the RT Y181C mutant A17 strain of HIV-1 and found to be >7-fold more effective than trovirdine and >1,400-fold more effective than nevirapine or delavirdine. Similarly, both HI-346 and HI-445 were more effective than trovirdine, nevirapine, and delavirdine against the problematic NNI-resistant HIV-1 strain A17-variant with both Y181C and K103N mutations in RT, although their activity was markedly reduced against this strain. Neither compound exhibited significant cytotoxicity at effective concentrations (CC50 >100 microM). These findings establish the lead compounds HI-346 and HI-445 as potent inhibitors of drug-sensitive as well as multidrug-resistant stains of HIV-1. 相似文献
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Two new complexes, ([Ru(phen)(2)(6-OH-dppz)](2+)) (1) and ([Ru(phen)(2)(6-NO(2)-dppz)](2+)) (2) (phen=1,10-phenanthroline; 6-OH-dppz=6-hydroxyl-dipyrido[3,2-a:2',3'-c]phenazine; 6-NO(2)-dppz=6-nitro-dipyrido[3,2-a:2',3'-c]phenazine), have been synthesized and characterized by elemental analysis, ES-MS (electrospray mass spectra), (1)H NMR, UV-Vis (UV-visible) and CV (cyclic voltammetry). The DNA-binding behaviors of both complexes have been studied by spectroscopic methods and viscosity measurements. The results indicate that the two complexes all bind to calf thymus DNA (CT-DNA) in an intercalative mode, and the DNA-binding affinity of complex 2 is greater than that of complex 1. In addition, complex 1 can promote photocleavage of pBR322 DNA upon irradiation, whereas complex 2 can promote cleavage of pBR322 DNA both upon irradiation and in the dark, with more efficient cleavage occurring upon irradiation. Theoretical studies for these complexes have been also carried out with the density functional theory (DFT) method. The difference in the DNA-binding behaviors of the two complexes can be reasonably explained by the DFT calculations. 相似文献
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Wing-Sze Lee Leung-Shi Cheng Chi-Sing Lee Wing-Tak Wong 《Inorganica chimica acta》2004,357(15):4389-4395
Chiral N,O pyridine alcohols HL1-HL6 were used to form complexes with copper(II) ions. Ligands HL1 and HL2 formed complexes with copper(II) ions when Cu(OAc)2 and HL were refluxed in methanol/ethanol mixture. Ligand HL3 formed a complex with copper(II) when deprotonated with NaH and stirred in a Cu(II) acetate THF solution. Ligands HL4-HL6 did not form complexes with copper(II) under similar conditions. Two complexes, [Cu(L1)2] and [Cu(L2)2], were isolated as single crystals and characterized by X-ray crystallography. These complexes showed low catalytic activities in asymmetric reactions. However, they became active when reacted with triflic acid. Copper complexes, [Cu(L)] or [Cu(L)]+, formed in situ by reacting ligands HL with copper(I) or (II) ions, respectively, were also found to be active copper catalysts for asymmetric cyclopropanation of styrene with ethyl diazoacetate and allylic oxidation of cyclohexene with t-butylperoxybenzoate. Enantioselectivities up to 56% and 38% were obtained in asymmetric cyclopropanation of styrene and asymmetric allylic oxidation of cyclohexene, respectively. 相似文献
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3'-Exonuclease resistance of DNA oligodeoxynucleotides containing O6-[4-oxo-4-(3-pyridyl)butyl]guanine
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Tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is a chemical carcinogen thought to be involved in the initiation of lung cancer in smokers. NNK is metabolically activated to methylating and pyridyloxobutylating species that form promutagenic adducts with DNA nucleobases, e.g. O6-[4-oxo-4-(3-pyridyl)butyl]guanine (O6-POB-dG). O6-POB-dG is a strongly mispairing DNA lesion capable of inducing both G→A and G→T base changes, suggesting its importance in NNK mutagenesis and carcinogenesis. Our earlier investigations have identified the ability of O6-POB-dG to hinder DNA digestion by snake venom phosphodiesterase (SVPDE), a 3′-exonuclease commonly used for DNA ladder sequencing and as a model enzyme to test nuclease sensitivity of anti-sense oligonucleotide drugs. We now extend our investigation to three other enzymes possessing 3′-exonuclease activity: bacteriophage T4 DNA polymerase, Escherichia coli DNA polymerase I, and E.coli exonuclease III. Our results indicate that, unlike SVPDE, 3′-exonuclease activities of these three enzymes are not blocked by O6-POB-dG lesion. Conformational analysis and molecular dynamics simulations of DNA containing O6-POB-dG suggest that the observed resistance of the O6-POB-dG lesion to SVPDE-catalyzed hydrolysis may result from the structural changes in the DNA strand induced by the O6-POB group, including C3′-endo sugar puckering and the loss of stacking interaction between the pyridyloxobutylated guanine and its flanking bases. In contrast, O6-methylguanine lesion used as a control does not induce similar structural changes in DNA and does not prevent its digestion by SVPDE. 相似文献
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Stockley M Clegg W Fontana G Golding BT Martin N Rigoreau LJ Smith GC Griffin RJ 《Bioorganic & medicinal chemistry letters》2001,11(21):2837-2841
The first reported synthesis of the DNA-PK inhibitor 3-cyano-6-hydrazonomethyl-5-(4-pyridyl)pyrid-[1H]-2-one (OK-1035) is described. The structure of OK-1035 was validated by X-ray crystallography. An IC(50) value of 100 microM was determined for inhibition of DNA-PK, and this is approximately 12-fold higher than that reported previously. 相似文献