Bioorganic and medicinal chemistry (2020)
Update date:2022-08-11
Topics:
Bai, Weiqi
Cheng, Kai
Gao, Yan
Guo, Huifang
He, Wei
Li, Conggang
Li, Zhuorong
Wu, Cai
NDM-1 can hydrolyze nearly all available β-lactam antibiotics, including carbapenems. NDM-1 producing bacterial strains are worldwide threats. It is still very challenging to find a potent NDM-1 inhibitor for clinical use. In our study, we used a metal-binding pharmacophore (MBP) enriched virtual fragment library to screen NDM-1 hits. SPR screening helped to verify the MBP virtual hits and identified a new NDM-1 binder and weak inhibitor A1. A solution NMR study of 15N-labeled NDM-1 showed that A1 disturbed all three residues coordinating the second zinc ion (Zn2) in the active pocket of NDM-1. The perturbation only happened in the presence of zinc ion, indicating that A1 bound to Zn2. Based on the scaffold of A1, we designed and synthesized a series of NDM-1 inhibitors. Several compounds showed synergistic antibacterial activity with meropenem against NDM-1 producing K. pneumoniae.
View MoreShuanghe Bio-Technology Limited
Contact:+86-571-61710758,18968016640
Address:Jinqiao north road 916# Fuyang
Beijing Huikang Boyuan Chemical Tech Co.,LTD
Contact:+86-10-68862197
Address:No.7 Haiying Road,Science City,Fengtai District,Beijing,China
Shanghai Forever Synthesis Co.,Ltd.
Contact:021-61124658
Address:Zhoukang Road,Pudong New District,Shanghai,China
Fusilin chemical science & technology co., ltd.
Contact:532-80698166/86057573, +86-400-669-7885
Address:School of Material Science & Engineering, Shandong Uinversity of Science & Technology, Huangdao Zone, Qindao, Shandong
website:http://www.sjzthld.com
Contact:86-311-66699812
Address:NO.600 ZHONGSHAN EAST ROAD SHIJIAZHUANG
Doi:10.1016/j.bioorg.2020.104476
(2021)Doi:10.1002/anie.202107903
(2021)Doi:10.1016/0584-8539(90)80251-S
(1990)Doi:10.1007/s11164-018-3557-z
(2018)Doi:10.1055/s-0039-1690781
(2020)Doi:10.1055/s-0035-1561296
(2016)