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


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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.

About the authors

Emerson da Silva

, Instituto de Tecnologia em Fármacos, Farmanguinhos, Fiocruz – Rua Sizenando Nabuco

Email: info@benthamscience.net

Gabriel de Andrade

Organic Synthesis, Instituto de Tecnologia em Fármacos, Farmanguinhos, Fiocruz – Rua Sizenando Nabuco

Email: info@benthamscience.net

Maria Lourenço

biology, Instituto Nacional de Infectologia, INI, Fiocruz

Email: info@benthamscience.net

Marcus De Souza

Instituto de Tecnologia em Fármacos, Farmanguinhos, Fiocruz – Rua Sizenando Nabuco

Author for correspondence.
Email: info@benthamscience.net

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