Effective natural inhibitors targeting LSD1 by computational study

Abstract

Abstract Objective: This study aimed to screen lead compounds and drug candidates with an inhibitory effect on the function of LSD1 from the ZINC database. Methods: We used computer-aided virtual technology to screen some agents that inhibit the function of LSD1. Initially, LibDock screened out some optimal compounds for docking with LSD1. These candidate compounds were subjected to ADME analysis (adsorption, distribution, metabolism, and excretion) and toxicity metrics. Molecular docking can determine the binding affinity between LSD1 and the ligand, and lastly, we applied molecular dynamics simulations to calculate the docking of the ligand-receptor complex. Results: Two natural compounds, ZINC000001651126 and ZINC000000001083, found in the ZINC database, are potent inhibitors of LSD1. When ZINC000001651126 and ZINC000000001083 bind to LSD1, they show high binding affinity. They are not hepatotoxic and have a high tolerance to cytochrome P4502D6. In addition, ZINC000001651126 and ZINC000000001083 have less developmental toxicity potential, rodent carcinogenicity, and Ames mutagenicity. Conclusions: ZINC000001651126 and ZINC000000001083 can be considered safe and ideal drug candidates for LSD1 inhibitors. This study can provide new ideas for future research and the application of LSD1 inhibitors.