Abstract：In order to evaluate the antituberculous activities of leading compound E in vitro and provide the evidence for further studies, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of compound E , isoniazid (INH) and rifampicin (RIF) against Mycobacterium tuberculosis H37Ra were determined by standard methods. Synergy between compound E and INH/RIF was determined by chequerboard titration in 96-well microtitre plates. According to MICs of the drugs alone and in combination , the fractional inhibitory concentration index (FICI) was calculated to find out that if there was synergy between the drugs. The elimination rate of non-growing H37Ra under normal as well as hypoxic and acidic conditions were determined by drug exposure in 3 days. Drug-resistant mutants of H37Ra and drug-resistant frequencies were obtained by Middlebrook 7H10-ADC agar containing compound E or INH.The results indicated that compound E was active against H37Ra with MIC of 0.078μg/ml ， and MBC of 0.312μg/ml. There was an additive effect between compound E and INH (FICI = 0.6) and a synergistic effect between E and RIF (FICI = 0. 27). The results also indicated that compound E showed better antituberculous activity against 10-day-old H37Ra than 6-week-old H37Ra under normal growth condition, but more active against 2-month-old H37Ra than 3-week-old H37Ra under hypoxic and acidic condition. No H37Ra resistant to compound E was detected after three independent repeats while the INH-resistant frequency was 3.4 x 10-6.
滕丽艳1，刘霞2，张雪莲1，王洪海1. 新型先导化合物E体外抗结核分枝杆菌活性的研究[J]. 微生物与感染
, 2012, 7(4): 208-212.
TENG Li-Yan1, LIU Xia2, ZHANG Xue-Lian1, WANG Hong-Hai1. Characterization of a new leading compound against Mycobacterium Tuberculosis H37Ra in vitro. Journal of Microbes and Infections, 2012, 7(4): 208-212.
