Synergistic activities of antituberculous drugs with cerulenin and trans-cinnamic acid against Mycobacterium tuberculosis.
Synergistic activities of antituberculous drugs with cerulenin and trans-cinnamic acid against Mycobacterium tuberculosis.
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DOI：
10.1111/j.1574-695x.1998.tb01161.x
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发表时间：
1998-06
影响因子：
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通讯作者：
Nalin Rastogi;K. S. Goh;L. Horgen;W. W. Barrow-W.
中科院分区：
文献类型：
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作者：
Nalin Rastogi;K. S. Goh;L. Horgen;W. W. Barrow-W.
最近结核病发病率急剧上升，大量出现耐多药病例，这使人们更加重视发现有效的新药和提高现有抗结核分枝杆菌药物潜力的战略。在本研究中，我们研究了蓝蓝蛋白和反式肉桂酸，它们最近被证明可以增强各种抗生素对鸟分枝杆菌的活性。药物化学，38(1994)2287-2295]，以提高异烟肼，利福平，氧氟沙星，阿米卡星和氯法齐明对结核分枝杆菌的活性。观察到的协同作用与使用乙胺丁醇的相同组合进行了比较，乙胺丁醇是一种用于标准抗结核化疗的细胞壁抑制药物。结果表明，乙胺丁醇在12/30的药物组合中具有增效作用，而蓝草蛋白为15/36，反式肉桂酸为101/18。这种药物活性的增加甚至在耐药分离株中也观察到。使用新型抗菌剂和了解其作用机制可能是确定以前未描述的靶点的有效策略，用于未来的药物开发。
The recent upsurge in the incidence of tuberculosis with significant emergence of multidrug-resistant cases has focused on the priority of discovering effective new drugs and on the strategies to augment the potential of existing drugs against Mycobacterium tuberculosis. In the present study, we investigated cerulenin and trans-cinnamic acid, which have recently been shown to augment the activity of various antibiotics against Mycobacterium avium [Antimicrob. Agents Chemother. 38 (1994) 2287-2295], to enhance the activity of isoniazid, rifampin, ofloxacin, amikacin and clofazimine against M. tuberculosis. The synergy observed was compared with identical combinations using ethambutol, a cell wall-inhibiting drug used in standard antituberculous chemotherapy. The results showed that ethambutol resulted in synergistic activity in 12/30 drug combinations, as compared to 15/36 for cerulenin and 101/18 for trans-cinnamic acid. This increase in drug activity was even observed with drug-resistant isolates. Use of novel antimicrobials and understanding of their mechanisms of action may be an effective strategy to determine previously undescribed targets for future drug development.