Open AccessDesign and identification of two novel resveratrol derivatives as potential LSD1 inhibitors
Author(s) -
Yongtao Xu,
Yunzhen Gao,
Min Yang,
Meiting Wang,
Jun Lü,
Zi-Qing Wu,
Junqiang Zhao,
Yi Yu,
Chang Wang,
Zongya Zhao,
Qinghe Gao,
Ying-Chao Duan,
Dayong Han
Publication year - 2021
Publication title -
future medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.708
H-Index - 69
eISSN - 1756-8927
pISSN - 1756-8919
DOI - 10.4155/fmc-2021-0105
Subject(s) - resveratrol , anticancer drug , bioavailability , docking (animal) , chemistry , pharmacology , computational biology , drug , molecular dynamics , drug development , in vitro , adme , combinatorial chemistry , biochemistry , biology , computational chemistry , medicine , nursing
Background: Overexpression of LSD1 is associated with the occurrence of many diseases, including cancers, which makes LSD1 a significant target for anticancer drug research. Methodology & Results: With the aid of 3D quantitative structure–activity relationship models established with 34 reported resveratrol derivative LSD1 inhibitors, derivatives 35–40 were designed. Absorption, distribution, metabolism and excretion calculations showed that they may have good bioavailability and drug likeness. Additionally, 35 and 37 presented good antitumor effects in an in vitro antiproliferative assay. Molecular docking and molecular dynamics simulation results indicated that 35 and 37 can establish extensive interactions with LSD1. Conclusion: The results of computational prediction and experimental validation suggest that 35 and 37 are effective antitumor inhibitors, which provides some ideas and directions for the development of new anticancer LSD1 inhibitors.