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Letters in Organic Chemistry

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ISSN (Print): 1570-1786
ISSN (Online): 1875-6255

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Letter Article

Synthesis and Anti-bacterial Activity Evaluation against Mycobacterium tuberculosis of New Quinoline Derivatives Coupled with the Camphor Nucleus

Author(s): Gabriel F. de Andrade, Emerson T. da Silva, Maria C.S. Lourenço, Solange M.S.V. Wardell, James L. Wardell and Marcus V.N. de Souza*

Volume 21, Issue 2, 2024

Published on: 06 October, 2023

Page: [107 - 115] Pages: 9

DOI: 10.2174/1570178620666230818092746

Price: $65

Abstract

Tuberculosis is a serious infectious disease caused by Mycobacterium tuberculosis (Mtb), also known as Koch’s bacillus. The involvement of latent forms and resistant strains has aggravated the situation, making the disease a serious public health problem.

The objective of the study was to synthesize and evaluate ten new compounds containing camphor nucleus coupled to quinolinic derivatives as probable inhibitors of sensitive and resistant strains of Mtb growth.

The synthesis of the final compounds, 3a-e and 4a-e, was based on the use of intermediates previously obtained, in which the coupling of the camphor nucleus to quinoline derivatives was carried out via a convergent route, which resulted in good yields (50-80%). All the final compounds were fully characterized, and the 3-dimensional molecular structure of compound 4c was determined. The antimycobacterial activities of all compounds against Mtb strains were evaluated and the cytotoxicity test was conducted using the in vitro microplate procedure with broth microdilution assay (MTT).

Compound 3e was the most active against sensitive and resistant strains, with a minimal inhibitory concentration (MIC) of 9.5 μM similar to ethambutol, a first-line drug used against the tuberculosis. The most active compound 3e was selected for the potential activity against Vero cells and it displayed no cytotoxicity at a concentration near the MIC value.

The final compounds were obtained in good yields, with derivative 3e being the most promising with high activity and low cytotoxicity. Such findings open new perspectives for drug development based on the incorporation of camphor nucleus in selected compounds.

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