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| Characterization of a new leading compound against Mycobacterium Tuberculosis H37Ra in vitro |
| TENG Li-Yan1, LIU Xia2, ZHANG Xue-Lian1, WANG Hong-Hai1 |
| State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, China |
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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.
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Received: 23 June 2012
Published: 25 December 2012
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Corresponding Authors:
WANG Hong-Hai , ZHANG Xue-Lian
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