Rational design, synthesis and antitubercular evaluation of novel 2-(trifluoromethyl)phenothiazine-[1,2,3]triazole hybrids

Abstract

Molecular hybridization is an emerging structural modification tool to design molecules with better pharmacophoric properties. A series of novel 2-(trifluoromethyl)phenothiazine-1,2,3-triazoles 5a-v designed by hybridizing two antitubercular drugs trifluoperazine and I-A09 in a single molecular architecture, were synthesized in very good yields using click chemistry. Among the all '22' compounds screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (Mtb), three analogs 5c, 5l and 5o were found to be most potent (MIC: 6.25μg/mL) antitubercular agents with good selectivity index.

Keywords: Antimycobacterial activity; Molecular hybridization; Mycobacterium tuberculosis; Phenothiazine; Triazoles.