Synthesis and Anti-bacterial Activity of New Substituted 2-trifluoromethyl-4-quinolinylhydrazone Analogs against Mycobacterium tuberculosis Strains

Abstract

Background: Tuberculosis (TB) is a serious disease that still affects humanity, despite being old, caused by the bacterium Mycobacterium tuberculosis (Mtb). The emergence of drug-resistant strains has alarmed governments and international organizations, such as the World Health Organization (WHO). The need for research on new drugs that are effective in a shorter treatment time and active against resistant strains still persists.

Objective: The objective of this study is to synthesize and evaluate forty-four substituted 2-trifluoromethyl-4-quinolinylhydrazone analogs, as probable inhibitors of Mycobacterium tuberculosis growth.

Methods: The anti-mycobacterial activities of all tested compounds against Mycobacterium tuberculosis strains, as well as the cytotoxicity test, were evaluated using the in vitro microplate procedure with broth microdilution assay.

Results: Thirteen compounds exhibited some activity against sensitive strain ATCC 27294, six of which were the most active: 4a, 4c, 6a, 6b, 6c, and 6g; with MIC around 7 - 8 μM, close to that presented by ethambutol (15.9 μM), a drug used in the treatment of tuberculosis. These same compounds also were active against a resistant strain of Mtb (T113), with MIC around 7 - 8 μM. Three of these compounds 4a, 6a, and 6c were not cytotoxic against Vero cells at concentrations near the MIC.

Conclusion: This study indicates the importance of the hydrazone function to obtain promising anti-TB compounds and open new perspectives for drug development.

Keywords: Mycobacterium tuberculosis; Quinolinylhydrazone; anti-bacterial activity; cytotoxicity.; resistant strain; tuberculosis.