Subhedar Dnyaneshwar D, Shaikh Mubarak H, Nawale Laxman, Sarkar Dhiman, Khedkar Vijay M, Shingate Bapurao B
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431 004, India.
Combichem Bioresource Centre, National Chemical Laboratory, Pune 411 008, India.
Bioorg Med Chem Lett. 2017 Feb 15;27(4):922-928. doi: 10.1016/j.bmcl.2017.01.004. Epub 2017 Jan 5.
A series of quinoline incorporated monocarbonyl curcumin analogues was efficiently synthesized using [HDBU][HSO] as catalyst via Knoevenagel type condensation and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG in dormant state. The analogues 3e, 3h, 4a and 4e exhibited very good antitubercular activity. The antiproliferative activity of the analogues against MCF-7, A549 and HCT-116 cell lines was evaluated using modified MTT assay and these compounds were found to be non-cytotoxic. Molecular docking study has been carried out against M. tuberculosis pantothenate synthetase (MTB PS) enzyme in an effort to enhance the understanding of their action as antitubercular agents. The potency, low cytotoxicity and selectivity of these analogues support them as valid leads for further optimization.
使用[HDBU][HSO]作为催化剂，通过Knoevenagel型缩合反应高效合成了一系列含喹啉的单羰基姜黄素类似物，并对其针对处于休眠状态的结核分枝杆菌H37Ra（MTB）和牛分枝杆菌卡介苗（Mycobacterium bovis BCG）的体外抗结核活性进行了评估。类似物3e、3h、4a和4e表现出非常好的抗结核活性。使用改良的MTT法评估了这些类似物对MCF-7、A549和HCT-116细胞系的抗增殖活性，发现这些化合物无细胞毒性。针对结核分枝杆菌泛酸合成酶（MTB PS）酶进行了分子对接研究，以努力加深对其作为抗结核药物作用的理解。这些类似物的效力、低细胞毒性和选择性支持它们作为进一步优化的有效先导物。
