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In vitro activity of isoimperatorin, alone and in combination, against M ycobacterium tuberculosis
Author(s) -
Guo N.,
Wu J.,
Fan J.,
Yuan P.,
Shi Q.,
Jin K.,
Cheng W.,
Zhao X.,
Zhang Y.,
Li W.,
Tang X.,
Yu L.
Publication year - 2014
Publication title -
letters in applied microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.698
H-Index - 110
eISSN - 1472-765X
pISSN - 0266-8254
DOI - 10.1111/lam.12195
Subject(s) - in vitro , mycobacterium tuberculosis , microbiology and biotechnology , tuberculosis , biology , virology , chemistry , medicine , biochemistry , pathology
Previous studies have shown that isoimperatorin ( IO ), a furanocoumarin isolated from several medicinal plants, has antimycobacterial activity against M ycobacterium 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 ( MIC s) of 50–100 μ g ml −1 and 100–200 μ g 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. Significance and Impact of the Study 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 M yco. 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.