康乐霉素A体外抗结核活性的初步研究

Preliminary studies on inhibitory activity of Kanglemycin A,against Mycobacterium tuberculosis

目的发现新安莎类抗生素，康乐霉素A体外抗结核活性。方法应用色谱技术从地中海诺卡氏菌康乐变株1747-64发酵液中分离康乐霉素A，并采用试管二倍稀释法，进行康乐霉素A对耻垢分枝杆菌（ATCC14468），结核分枝杆菌H37Rv（ATCC27294），H37Ra（ATCC25177），临床分离的氧氟沙星（OFLX）敏感结核分枝杆菌以及临床分离的耐氧氟沙星结核分枝杆菌最低抑制浓度（Minimal Inhibitor Concentration，MIC）的试验。结果康乐霉素A对耻垢分枝杆菌活性弱，MIC为64μg／ml，对结核分枝杆菌H37Rv，H37Ra的MIC为8μg／ml，对临床分离的氧氟沙星敏感结核分枝杆菌菌株的MIC范围为1～8μg／ml，临床分离的耐氧氟沙星结核分枝杆菌菌株的MIC范围为1～16μg／ml。结论新安莎类抗生素，康乐霉素A体外具有明显的抗结核活性，有望成为新抗结核药物或先导化合物。

Objective To explore the bioactivities of Kanglemycin A, a novel ansamycin group antibiotic against M. tuberculosis（TB）in vitro. Methods Kanglemycin A was purified by silica gel chromatography and sephadex LH-20 chromatography, and its MICs to 20 strains including M. smegrnatis, M. tuberculosis H37Rv, M. tuberculosis H37Ra, ofloxacin （OFLX）-sensitive M. tuberculosis clinical isolates and OFLX-resistant M. tuberculosis isolates were determined by equivalent serial dilution method. Results Kanglemycin A MIC to M. smegmatis was 64μg/ml, to M. tuberculosis H37Rv and H37Ra was 8μg/ml, to OFLX-sensitive M. tuberculosis isolates were 1-8μg/ml, to OFLX-resistant M. tuberculosis isolates were 1-16μg/ml. Conclusion Kanglemycin A had strong inhibitory activity against M. tuberculosis, and might be a potential anti-TB drug candidate or leading compound.