以脂肪酸合成酶FabH为靶标的化合物体外抗结核作用的初步研究

The study on antimycobacterial activities in vitro of the compounds that target Mycobacterium tuberculosis fabH

目的研究结核分枝杆菌脂肪酸合成酶FabH为靶标的化合物的体外抗结核活性，研制新的高效、安全的抗结核药物。方法以平板滤纸法测定化合物对草分枝杆菌的抑菌圈，以试管抑菌法检测化合物对结核分枝杆菌药物敏感株和耐多药分离株的抑制作用。结果18种化合物在500μmol／L浓度时对草分枝杆菌的抑菌圈为1．8～2．4cm，其中7种化合物在250μmol／L和125μmol／L浓度时对草分枝杆菌的抑菌圈为1．5～2．2cm。结核分枝杆菌H37Rv标准株在分别含3mmol／L的18种化合物的培养基上培养2周时，绝大多数含化合物培养基上未见细菌生长；培养4周时，No．115、No．131、No．128、No．129、No．137化合物的抑菌作用较明显。结核分枝杆菌耐多药分离株HB240在分别含3mmol／L的11种化合物的培养基上培养2周和4周时，No．115化合物均显示明显的抑菌作用。结论以脂肪酸合成酶FabH为靶标的大多数化合物在体外都具有不同程度的抗结核活性，尤其是No．115化合物对草分枝杆菌、结核分枝杆菌敏感株和耐药株都具有明显的抑制作用。

Objective To study antimycobacterial activities in vitro of the compounds that target Mycobacterium tuberculosis β-ketoacyl-acyl carrier protein （ACP） synthase m （FabH）, and to obtain a novel, effective, and safe antitubereulous agent. Methods The inhibitory diameters of compounds effect on M. phlei on agar plate were determined. The inhibitory effect of compounds on M. tuberculosis strain H37Rv and MDR-strain was tested on L-J media. Results The inhibitory diameters of 18 kinds of 500/μmol/L compounds effect on M. phlei on agar plate were 1.8 to 2.4 cm, respectively. The inhibitory diameters of 7 kinds of 250/μmol and 125μmol compounds effect on M. phlei on agar plate were 1.5 to 2.2cm, respectively. 18 kinds of 3 mmol/L compounds inhibited obviously the growth of M. tuberculosis strain H37 Rv on L-J media at 2 weeks, and the compounds No. 115, No. 131, No. 128, No. 129, and No. 137 also inhibited at 4 weeks. The compounds No. 115 exhibited obvious inhibitory activity on M. tuberculosis MDR-strain HB240 inoculated on L-J media containing 11 kinds of compounds for 2 weeks and 4 weeks, respectively. Conclusion The most of compounds targeted fatty acid synthase FabH exhibited different degree of antimycobacterial activities, especially compounds No. 115had obvious inhibitory effect on M. phlei, M. tuberculosis strain H37Rv and MDR-strain HB240.