Synthesis, Characterization, and In Vitro Evaluation of New Amino‐Alcohol Quinolines as Promising Antimycobacterial Agents

Abstract

Nontuberculous mycobacteria (NTM) mainly Mycobacterium avium complex (MAC), are emerging pathogens responsible for pulmonary infections. Therefore, the effectiveness of the gold standard treatment is compromised by the emergence of intrinsic and acquired resistance of MAC. In this context, seventeen amino‐alcohol quinolines as mefloquine analogs were developed as part of this work. Studies on the physicochemical properties, cytotoxicity and activity of these quinoline‐based compounds, in relation to their structures, highlighted the important role of the trifluoromethyl and piperazine moieties. Thus, (R)‐4c was identified as the most promising anti‐MAC compound with the highest selectivity index value of 5.8. It was tested, in two‐drug combinations, using a checkerboard assays with the standard antibiotics (clarithromycin, rifampicin and ethambutol), demonstrating an additive effect with each antibiotic of this gold standard treatment. These results confirm the potential of amino‐alcohol quinolines as alternative of current anti‐NTM agents.