Bioorganic and Medicinal Chemistry Letters p. 2338 - 2344 (2019)
Update date:2022-08-25
Topics:
Shaikh, Mahamadhanif S.
Kanhed, Ashish M.
Chandrasekaran, Balakumar
Palkar, Mahesh B.
Agrawal, Nikhil
Lherbet, Christian
Hampannavar, Girish A.
Karpoormath, Rajshekhar
InhA (Enoyl-ACP reductase) plays a crucial role in the biosynthetic pathway of cell wall synthesis in Mycobacterium tuberculosis (Mtb). Isoniazid (INH) is an important first-line drug, which inhibits InhA. The rapid increase in resistance to INH and currently marketed drugs as well as emergence of MDR-TB and XDR-TB has complicated the diagnosis and treatment of Mtb with ever increasing threat to human kind. Herein, we report novel N-methyl carbazole derivatives as potential anti-TB compounds acting directly via InhA inhibition. All the synthesized final compounds were screened against Mtb virulent cell line H37Rv and investigated the InhA enzyme inhibition. Interestingly, compound 9e displayed promising inhibition (91%) at 50 μM concentration and IC50 of 2.82 μM against InhA. To understand the ligand receptor interaction between compound 9e and InhA, molecular docking and molecular dynamics experiments were performed. The computational results were in agreement with the observed experimental data. Further, the cytotoxicity studies on mammalian cells revealed that all the compounds were safe.
View MoreSuzhou Howsine Biological Technology Co.,Ltd
website:http://www.howsine.com
Contact:86-512-67262751
Address:No 3,Weihua Road ,Suzhou Industrial Park ,Jiangsu ,China.
Hangzhou Haiqiang Chemical Co.,Ltd.
Contact:+86-571-86960370
Address:Add: 5/F, Around Town North Road,No. 10, Hangzhou, Zhejiang,China
Contact:86-571-86737118-8689
Address:No.69, 12 Street, HEDA, Hangzhou, Zhejiang, China
Shandong Zhongcheng Barium Salt Co., Ltd
Contact:+86-15725732638
Address:No.29 baoxi road, hi-tech zone, zibo, shandong
Contact:86-21-57725962
Address:shanghai
Doi:10.1016/j.tet.2015.07.027
(2015)Doi:10.1039/c5cy00067j
(2015)Doi:10.1021/ic502119b
(2015)Doi:10.1016/S0040-4039(00)80202-6
(1988)Doi:10.1016/S0040-4039(00)72683-9
(1975)Doi:10.1016/j.electacta.2018.06.144
(2018)