Petkova Zhanina, Valcheva Violeta, Momekov Georgi, Petrov Petar, Dimitrov Vladimir, Doytchinova Irini, Stavrakov Georgi, Stoyanova Malinka
Institute of Organic Chemistry with Center of Phytochemistry, Bulgarian Academy of Sciences, Acad. Bonchev 9, Sofia 1113, Bulgaria.
Institute of Microbiology, Bulgarian Academy of Sciences, Akad. Bonchev 26, Sofia 1113, Bulgaria.
Eur J Med Chem. 2014 Jun 23;81:150-7. doi: 10.1016/j.ejmech.2014.05.007. Epub 2014 May 4.
A series of aminoalcohols were synthesized by reaction of aminolysis of camphor derived oxiranes with chosen amines. The compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv. Ten of the new structures show much higher activity than the classical anti-TB drug ethambutol. Some of the most active compounds were tested against MDR strain 43, and four of them demonstrated excellent activities with MICs 0.27-0.72 μM. The cytotoxicity of representative exerting antimycobacterial activity compounds was assessed. Quantitative structure-activity relationship (QSAR) model is derived to estimate the contribution of each structural fragment to the activity. The camphane-based aminoalcohols are promising lead compounds for further development of novel antimycobacterial agents.
通过樟脑衍生的环氧乙烷与选定的胺进行氨解反应合成了一系列氨基醇。对这些化合物针对结核分枝杆菌H37Rv的体外活性进行了评估。十种新结构显示出比经典抗结核药物乙胺丁醇更高的活性。一些活性最强的化合物针对多药耐药菌株43进行了测试，其中四种表现出优异的活性，最低抑菌浓度为0.27 - 0.72μM。评估了具有抗分枝杆菌活性的代表性化合物的细胞毒性。推导了定量构效关系（QSAR）模型以估计每个结构片段对活性的贡献。基于莰烷的氨基醇是进一步开发新型抗分枝杆菌药物的有前景的先导化合物。
