Organic Chemistry Division-II (CPC), CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, India.
Center for X-ray Crystallography, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, India.
Chem Biol Drug Des. 2018 Jul;92(1):1315-1323. doi: 10.1111/cbdd.13196. Epub 2018 May 18.
In the quest for new active molecules against Mycobacterium tuberculosis, a series of dihydroquinoline derivatives possessing triazolo substituents were efficiently synthesized using click chemistry. The structure of 6l was evidenced by X-ray crystallographic study. The newly synthesized compounds were evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv (ATCC27294). The compounds 6a, 6g, and 6j (MIC: 3.13 μg/ml) showed promising activity when compared to the first-line drug such as ethambutol. In addition, the structure and antitubercular activity relationship were further supported by in silico molecular docking studies of the active compounds against 3IVX.PDB (crystal structure of pantothenate synthetase in complex with 2-(2-(benzofuran-2-ylsulfonylcarbamoyl)-5-methoxy-1H-indol-1-yl)acetic acid).
在寻找对抗结核分枝杆菌的新型活性分子的过程中，我们使用点击化学高效合成了一系列具有三唑取代基的二氢喹啉衍生物。通过 X 射线晶体学研究证实了 6l 的结构。新合成的化合物对结核分枝杆菌 H37Rv（ATCC27294）进行了体外抗结核活性评估。与一线药物乙胺丁醇相比，化合物 6a、6g 和 6j（MIC：3.13μg/ml）表现出有希望的活性。此外，通过对活性化合物与 3IVX.PDB（与 2-（2-（苯并呋喃-2-基磺酰基）-5-甲氧基-1H-吲哚-1-基）乙酸的 pantothenate 合成酶复合物的晶体结构）进行计算机分子对接研究，进一步支持了结构与抗结核活性关系。
