Combining virtual screening and in vitro evaluation for the discovery of potential CYP11B2 inhibitors

Jiali Li; Na Yu; Hongmei Guo; YuanZe Shi; XiaoDie Chen; Jinping Wu; Xuemin Zhao; Mao Shu; Rui Wang; Zhihua Lin

doi:10.4155/fmc-2022-0119

Combining virtual screening and in vitro evaluation for the discovery of potential CYP11B2 inhibitors

Future Med Chem. 2022 Sep;14(17):1239-1250. doi: 10.4155/fmc-2022-0119. Epub 2022 Aug 1.

Authors

Jiali Li^{1

2}, Na Yu^{1

2}, Hongmei Guo^{1

2}, YuanZe Shi^{1

2}, XiaoDie Chen^{1

2}, Jinping Wu^{1

2}, Xuemin Zhao^{1

2}, Mao Shu^{1

2}, Rui Wang^{1

2}, Zhihua Lin^{1

2}

Affiliations

¹ School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, 400054, China.
² Key Laboratory of Screening and Activity Evaluation of Targeted Drugs, Chongqing, 400054, China.

PMID: 35912798
DOI: 10.4155/fmc-2022-0119

Abstract

Aim: To search for highly bioactive hits for CYP11B2 inhibitors by virtual screening and in vitro evaluation. Materials & methods: Virtual screening of potential CYP11B2 inhibitors was performed by molecular docking and molecular dynamics simulation. Compound activity was determined by in vitro evaluation using MTT and ELISA assays. Results & conclusion: Based on the results of molecular docking and molecular dynamics simulation, nine lead hits were selected for in vitro biochemical testing. All hits in in vitro experiments had lower inhibitory effects on cell proliferation and certain inhibitory effects on aldosterone secretion. These hits may be excellent candidates for CYP11B2 inhibitors.

Keywords: CYP11B2; biological activity; evaluation; inhibitor; virtual screening.

MeSH terms

Cytochrome P-450 CYP11B2* / chemistry
Cytochrome P-450 CYP11B2* / metabolism
Molecular Docking Simulation
Molecular Dynamics Simulation*

Substances

Cytochrome P-450 CYP11B2