Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

In vitro evaluation of the inhibitory effect of 3, 5-dichloro-2-pyridone on Mycobacterium tuberculosis H37Rv

Lin Ling¹, Chen Ling¹, Hua Wu¹

¹Department of Pharmacy, Binhu Hospital of Heifei City, The Third Affiliated Hospital of Anhui Medical University, Hefei 230031; ²Department of Reproductive Medicine Center, The First Affiliated Hospital of University of Science and Technology of China, Hefei 230001, China.

For correspondence:- Hua Wu Email: haileyadams435@yahoo.com Tel:+8655165758263

Accepted: 12 December 2019 Published: 01 February 2020

Citation: Ling L, Ling C, Wu H. In vitro evaluation of the inhibitory effect of 3, 5-dichloro-2-pyridone on Mycobacterium tuberculosis H37Rv. Trop J Pharm Res 2020; 19(1):163-168 doi: 10.4314/tjpr.v19i1.24

© 2020 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the anti-tuberculosis potential of twelve commercially available pyridone analogues against Mycobacterium tuberculosis H37Rv strain.

Methods: Twelve commercially available pyridone-based compounds were screened against M. tuberculosis H37Rv using different susceptibility tests. The most active or lead compound was further evaluated in detail for its anti-tuberculosis (anti-TB) potential. Kill kinetics was used to determine the dynamics of its anti-TB activity in vitro.

Results: Compounds d, j and k were potent against M. tuberculosis H37Rv, with minimum inhibitory concentrations (MICs) of 10, 5 and 10 µg/mL, respectively. The standard anti-TB drugs used in this study (positive control drugs) demonstrated MIC of 2.5 µg/mL. The anti-TB effect of compound j was comparable with those of the standard drugs (RIF, LVX, AMK, EMB and INH). The minimum bactericidal concentration (MBC) of compound j was 10 µg/mL. It produced an MIC of 5 µg/mL in agar proportion method (APM). However, its MIC in Middlebrook 7H9 broth supplemented with 10 % fetal bovine serum (FBS) and 4 % bovine serum albumin (BSA) increased 4- and 8-fold, respectively. The bactericidal effect of compound j was time- and concentration-dependent at dilutions above 2x MIC. Combination of compound j with RIF, LVX or AMK exhibited fractional inhibitory concentration index (ΣFIC) of 1, indicative of additive drug-drug interactions. However, combination with INH or EMB produced a ΣFIC of 2. None of the tested drug combinations was antagonistic.

Conclusion: Compound j exhibits potent time- and concentration-dependent antimicrobial effect against M. tuberculosis H37Rv. Thus, it may be suitable as an adjunct to current treatment of drug sensitive and drug-resistant TB.

Keywords: Tuberculosis, Mycobacterium tuberculosis, Pyridone analogs, Antimicrobial activity, Antibiotics