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1.
Bioorg Med Chem ; 23(19): 6317-26, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26344590

RESUMO

Two groups of benzimidazole derivatives were synthesized using as precursors 5(6)-substituted 2-mercapto-benzimidazol-thiols and their antioxidant activity was investigated using TBA-MDA test. In the group of 1,3-disubstituted-benzimidazol-2-imines the highest lipid peroxidation inhibition effect 74.04% (IC50=141.89 µg/mL) revealed ethyl [3-(2-ethoxy-2-oxoethyl)-2-imino-5-benzoyl-2,3-dihydro-1H-benzimdazol-1-yl]acetate 12 while in the group of 2-substituted-1,3-thiazolo[3,2-a]benzimidazolones the highest inhibition effect showed 2-(4-fluorobenzylidene)-7-(phenylcarbonyl)[1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one 17 90.76% (IC50=53.70 µg/mL). In order to estimate the capability of the studied benzimidazoles to act as radical scavengers the structure of the most active derivative within the both subseries was optimized at B3LYP/6-311++G(∗∗) level and the respective bond dissociation enthalpies were calculated. The appropriate models for the HAT and SET-mechanism of the antioxidant activity were proposed. The antibacterial activity of the compounds was evaluated against two Gram-positive bacteria (Bacillus subtilis ATCC 6633 and Staphylococcus aureus ATCC 6538) and three Gram-negative bacteria (Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 9027 and Salmonella abony NCTC 6017). 1,3-Diphenylpropyl-5-methyl-1,3-dihydro-2H-benzimidazol-2-imine 14 exhibited significant activity against B. subtilis, S. aureus, S. abony and E. coli (with MIC values of 0.125, 0.016, 0.50 and 0.50mg/mL, respectively). The group of thiazolobenzimidazolones did not reveal antibacterial activity against the tested strains.


Assuntos
Antibacterianos/síntese química , Benzimidazóis/química , Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Benzimidazóis/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Conformação Molecular , Estereoisomerismo , Relação Estrutura-Atividade , Termodinâmica
2.
Eur J Med Chem ; 41(12): 1412-20, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16996654

RESUMO

Piperazine derivatives of 5(6)-substituted-(1H-benzimidazol-2-ylthio)acetic acids were synthesized by using two methods and studied for antihelminthic activity. The antiparasitic screening showed that compounds 18-24 exhibited higher activity against Trichinella spiralis in vitro in comparison to methyl 5-(propylthio)-1H-benzimidazol-2-yl-carbamate (albendazole). Most active were compounds 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-1H-benzimidazole 21 and 2-{[2-oxo-2-(4-benzhydrylpiperazin-1-yl)ethyl]thio}-5(6)-methyl-1(H)-benzimidazole 19 as well as 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-5(6)-methyl-1(H)-benzimidazole 23 with efficacy of 96.0%, 98.4% and 100%, respectively. The tested derivatives 15-19 and 20-23 were less active against Syphacia obvelata in vivo than albendazole and exhibited the same efficacy as piperazine, but in twice lower concentration.Compounds 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-1H-benzimidazole 21, 1,4-bis[(5(6)-methyl-1(H)-benzimidazol-2-ylthio)acetyl]piperazine 17 and 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-5(6)-methyl-1(H)-benzimidazole 23 had higher efficacies of 73%, 76%, and 77%, respectively.


Assuntos
Anti-Helmínticos/farmacologia , Benzimidazóis/farmacologia , Oxyuroidea/efeitos dos fármacos , Trichinella spiralis/efeitos dos fármacos , Animais , Anti-Helmínticos/efeitos adversos , Anti-Helmínticos/síntese química , Anti-Helmínticos/química , Benzimidazóis/efeitos adversos , Benzimidazóis/síntese química , Benzimidazóis/química , Fígado/efeitos dos fármacos , Espectroscopia de Ressonância Magnética
3.
Bioorg Med Chem ; 13(19): 5550-9, 2005 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-16084100

RESUMO

Some new thiazolo[3,2-a]benzimidazolone derivatives were synthesized using two methods. The structures of the synthesized compounds were proved by means of IR, (1)H NMR and mass spectral data. Ab initio computations were performed in order to determine the electronic structure and geometry of the investigated molecules and to compare it to the geometry of albendazole. Biologically, experiments in vitro and in vivo were accomplished in order to identify the efficacy of the obtained thiazolobenzimidazolones against Trichinella spiralis. The effectiveness of compounds 4a-c in the intestinal phase of trichinellosis was 100% and in the muscle phase were 88% and 80% at a concentration of 100mg/kg mw for the compounds 4a and 4c. The results of the hepatotoxicity test showed that the compounds 4a and 4b possess hepatotoxicity comparable to that of albendazole.


Assuntos
Benzimidazóis/síntese química , Benzimidazóis/farmacologia , Tiazóis/síntese química , Tiazóis/farmacologia , Triquinelose/tratamento farmacológico , Triquinelose/prevenção & controle , Animais , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Hepatócitos/efeitos dos fármacos , Estrutura Molecular , Testes de Sensibilidade Parasitária , Ratos , Trichinella spiralis/efeitos dos fármacos , Triquinelose/metabolismo
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