In vitro evaluation of the inhibitory effect of 3, 5-dichloro-2- pyridone on Mycobacterium tuberculosis H37Rv
| Autor: | Chen Ling, Lin Ling, Hua Wu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Minimum bactericidal concentration
Tuberculosis food.ingredient biology medicine.drug_class Chemistry Antibiotics Middlebrook 7H9 broth Pharmaceutical Science Pharmacology biology.organism_classification Antimicrobial medicine.disease Mycobacterium tuberculosis chemistry.chemical_compound food medicine biology.protein Agar Pharmacology (medical) Bovine serum albumin |
| Zdroj: | Tropical Journal of Pharmaceutical Research. 19:163-168 |
| ISSN: | 1596-9827 1596-5996 |
| DOI: | 10.4314/tjpr.v19i1.24 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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