Synthesis and in vitro antimycobacterial and antileishmanial activities of hydroquinone-triazole hybrids

AbstractInfectious diseases such as tuberculosis and leishmaniasis are leading causes of human death. One of the major factors contributing to the poor control of these diseases is primarily the reduced effectiveness of the existing chemotherapies as result of the increasing rise of multidrug-resistant strains of their causative agents. This leads to the imperative need to develop new and effective drugs. In search for such agents, a series of hydroquinone-triazole hybrids was investigated. The design, synthesis, and biological activities against the human virulent H37Rv strain ofMycobacterium tuberculosis (Mtb) andLeishmaniasis major (L. major), causative pathogen of human cutaneous leishmaniasis, are herein reported. The hybrids were synthesized following a two-step process Michael addition and Click chemistry. They were found to be noncytotoxic toward human kidney embryonic cells but expressed poor cellular antileishmanial and antimycobacterial activities. Hybrid14, 2 ‐{4‐[(phenylsulfanyl)methyl]‐1H‐1,2,3‐triazol‐1‐yl}benzene‐1,4‐diol, was the most active among synthesized molecules, with MIC90 16 and IC50 23  µM againstMtb andL. major parasite, respectively, but had a poor safety profile, being as toxic to mammalian cells as to mycobacteria and parasites. Thus, compound14 did not stand as potential anti-infective hit for further investigation. Future endeavor will focus on the investigation of more rigid and flexible hybrids of both scaffolds in order...
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research