RESUMO
A library of seventeen novel 1,2,3-triazole derivatives were efficiently synthesized in excellent yields by the popular 'click chemistry' approach and evaluated in vitro for their anti-tubercular activity against Mycobacterium tuberculosis H37Ra (ATCC 25177 strain). Among the series, six compounds exhibited significant activity with minimum inhibitory concentration (MIC) values ranging from 3.12 to 0.78µg/mL and along with no significant cytotoxicity against MBMDMQs (mouse bone marrow derived macrophages). Molecular docking of the target compounds into the active site of DprE1 (Decaprenylphosphoryl-ß-d-ribose-2'-epimerase) enzyme revealed noteworthy information on the plausible binding interactions.
Assuntos
Antituberculosos/síntese química , Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Triazóis/química , Triazóis/farmacologia , Oxirredutases do Álcool/antagonistas & inibidores , Oxirredutases do Álcool/metabolismo , Animais , Antituberculosos/toxicidade , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Células da Medula Óssea/citologia , Domínio Catalítico , Química Click , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Simulação de Acoplamento Molecular , Mycobacterium tuberculosis/enzimologia , Relação Estrutura-Atividade , Termodinâmica , Triazóis/toxicidadeRESUMO
Herein we report a microwave assisted Ru(iii)/TBHP-mediated reaction of indoles with tetramethylurea (TMU) synthesizing symmetrical as well as unsymmetrical bis(indolyl)methanes, where TMU acts as a methylenating agent. This is the first report where TMU is used as a methylene source. Moreover, the synthesis of unsymmetrical bis(indolyl)methanes by using a carbon precursor is also reported herein for the first time. Various substituted indoles are used for the reaction. The reaction is high yielding and takes a much shorter time to accomplish compared to the existing methods.
