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Synthesis and Antibacterial Activity of Mefloquine-Based Analogs Against Sensitive and Resistant Mycobacterium tuberculosis Strains

A series of new 2,8-bis(trifluoromethyl)quinoline derivatives 2 - 9 were synthesized and evaluated for their in vitro antibacterial activity against sensitive Mycobacterium tuberculosis ATCC 27294, using the microplate Alamar Blue assay (MABA). The compounds 3c (37.2 µM), 7 (68.1 µM) and 9 (65.6 µM) showed the highest activity in this series with MIC values similar when compare to the standard Mefloquine (30 – 60 µM), being 3c the most potent. The more active compounds 3c, 7, and 9 were also evaluated against resistant strain SR 2571/0215 (resistant to Rifampicin and Isoniazid) displaying MIC of 37.2, 136.2 and 65.6 µM respectively. All compounds were tested against three cancer cell lines and showed low cytotoxicity. The compound 3c was the most potent against resistant and sensitive Mycobacterium tuberculosis in this series with important information and perspectives in the search of new bioactive compounds based on Mefloquine analogs.

Journal Title: Current Topics in Medicinal Chemistry

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