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  • In vitro activity of isoimperatorin, alone and in combination, against Mycobacterium tuberculosis.

In vitro activity of isoimperatorin, alone and in combination, against Mycobacterium tuberculosis.

Letters in applied microbiology (2013-12-18)
N Guo, J Wu, J Fan, P Yuan, Q Shi, K Jin, W Cheng, X Zhao, Y Zhang, W Li, X Tang, L Yu
ABSTRACT

Previous studies have shown that isoimperatorin (IO), a furanocoumarin isolated from several medicinal plants, has antimycobacterial activity against Mycobacterium tuberculosis strain H37Rv (ATCC 27294). This study demonstrated that IO has antimycobacterial activity against 2 drug-sensitive and 6 drug-resistant isolates, with minimum inhibitory concentrations (MICs) of 50-100 μg ml(-1) and 100-200 μg ml(-1), respectively. IO exhibited synergistic antimycobacterial effects with rifampin (RMP), isoniazid (INH) and ethambutol (EMB) against 6 drug-resistant strains, with fractional inhibitory concentration index (FICI) values of 0·133-0·472, 0·123-0·475 and 0·124-0·25, respectively. The IO/RMP, IO/INH and IO/EMB combination treatments had synergistic effects or no interaction in the 2 drug-sensitive strains and the standard strain ATCC 27294. The synergism of combined drugs against drug-resistant strains was better than drug-sensitive strains. No antagonism was observed in with the aforementioned combinations against all strains tested. IO exhibited relatively low cytotoxicity to Vero cells. Our results indicate that IO may serve as promising a template for future antimycobacterial drug development. This is the first report on the in vitro synergistic antimycobacterial effects of isoimperatorin (IO) in combination with three first-line drugs: rifampin (RMP), isoniazid (INH) and ethambutol (EMB). The results indicated that the antimycobacterial activity of IO was modest; however, IO was a useful and effective agent against Myco. tuberculosis when it was combined with first-line antimycobacterial drugs and is worthy of further development as a lead compound for the development of novel antimycobacterial therapeutic agents.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Rifampicin, ≥95% (HPLC), powder or crystals
Sigma-Aldrich
Ethambutol dihydrochloride, antimycobacterial
Sigma-Aldrich
Rifampicin, suitable for plant cell culture, BioReagent, ≥95% (HPLC), powder or crystals
Ethambutol hydrochloride, European Pharmacopoeia (EP) Reference Standard
Rifampicin, European Pharmacopoeia (EP) Reference Standard
Supelco
Isoniazid, analytical standard, ≥99% (TLC)
Ethambutol for system suitability, European Pharmacopoeia (EP) Reference Standard
Isoniazid, European Pharmacopoeia (EP) Reference Standard