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1.
Bioorg Chem ; 100: 103955, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32464405

RESUMO

A series of thirty one novel 2-(((1-(substituted phenyl)-1H-1,2,3-triazol-4-yl)methoxy)carbonyl)-3-methylquinoxaline-1,4-dioxide (7a-l), 3-(((1-(substituted phenyl)-1H-1,2,3-triazol-4-yl)methoxy)carbonyl)-6-chloro-2-methylquinoxaline-1,4-dioxide (8a-l) and 2-(((1-(substituted phenyl)-1H-1,2,3-triazol-4-yl)methoxy)carbonyl)-6,7-dichloro-3-methylquinoxaline-1,4-dioxide (9a-g) analogues were synthesized, characterized using various analytical techniques and single crystal was developed for the compounds 8 g and 9f. Synthesized compounds were evaluated for in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain and two clinical isolates Spec. 210 and Spec. 192. The titled compounds exhibited minimum inhibitory concentration (MIC) ranging from 30.35 to 252.00 µM. Among the tested compounds, 8e, 8 l, 9c and 9d exhibited moderate activity (MIC = 47.6 - 52.0 µM) and 8a exhibited significant anti-tubercular activity (MIC = 30.35 µM). Furthermore, 8e, 8 l, and 9d were found to be less toxic against human embryonic kidney, HEK 293 cell lines. Finally, a docking study was also performed using MTB DNA Gyrase (PDB ID: 5BS8) for the significantly active compound 8a to know the exact binding pattern within the active site of the target enzyme.


Assuntos
Antituberculosos/química , Óxidos/química , Quinoxalinas/química , Triazóis/química , Antituberculosos/metabolismo , Antituberculosos/farmacologia , Sítios de Ligação , Domínio Catalítico , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , DNA Girase/química , DNA Girase/metabolismo , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Células HEK293 , Humanos , Testes de Sensibilidade Microbiana , Conformação Molecular , Simulação de Acoplamento Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Óxidos/metabolismo , Óxidos/farmacologia , Quinoxalinas/metabolismo , Quinoxalinas/farmacologia , Relação Estrutura-Atividade , Triazóis/metabolismo , Triazóis/farmacologia
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