Synthesis and antimycobacterial activity of disubstituted benzyltriazoles

AbstractThe increasing prevalence of multidrug-resistant strains ofMycobacterium tuberculosis (Mtb), the pathogen of human tuberculosis (TB), serves as a strong incentive for the discovery and development of new agents for the treatment of this plight. In search for such drugs, we investigated a series of benzyltriazole derivatives. We herein report the design, synthesis and biological activity of disubstituted benzyltriazoles against the human virulent H37Rv strain ofMtb as well as the toxicity on human embryonic kidney (HEK-293) cells. The derivative21 featuring trifluoromethyl substituent inpara position on the phenyl ring andn-butyl chain in position 4 on the triazole ring was the most active with MIC90 and MIC99 values of 1.73 and 3.2  µM, respectively, in the albumin-free medium. It also displays high selectivity towards bacteria growth inhibition (SI >  58), thus stands as a better hit for further investigation, including lead optimization, DMPK parameters determination and assessment of its activity in animal models.
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research