Abstract

Molecular hybridisation of four bioactive fragments piperazine, substituted-benzofuran, amino acids, and 2,4-dinitrobenzenesulfonamide as single molecular architecture was designed. A series of new hybrids were synthesised and subjected to evaluation for their inhibitory activity against Mycobacterium tuberculosis (Mtb) H37Rv. 4d–f and 4o found to exhibit MIC as 1.56 µg/mL, equally active as ethambutol whereas 4a, 4c, 4j displayed MIC 0.78 µg/mL were superior to ethambutol. Tested compounds demonstrated an excellent safety profile with very low toxicity, good selectivity index, and antioxidant properties. All the newly synthesised compounds were thoroughly characterised by analytical methods. The result was further supported by molecular modelling studies on the crystal structure of Mycobacterium tuberculosis enoyl reductase.

摘要

设计了四种生物活性片段哌嗪、取代苯并呋喃、氨基酸和2,4-二硝基苯磺酰胺的分子杂交作为单分子结构。合成了一系列新的杂交体，并对其对结核分枝杆菌( Mtb ) H37Rv 的抑制活性进行了评估。4d – f和4o的 MIC 为 1.56 µg/mL，与乙胺丁醇活性相同，而4a、4c、4j的 MIC 为 0.78 µg/mL，优于乙胺丁醇。测试的化合物表现出优异的安全性、极低的毒性、良好的选择性指数和抗氧化特性。所有新合成的化合物均通过分析方法进行了彻底表征。该结果得到了结核分枝杆菌烯酰还原酶晶体结构的分子模型研究的进一步支持。