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Pharmacophore‐based virtual screening, molecular docking, molecular dynamics simulation, and biological evaluation for the discovery of novel BRD 4 inhibitors
Author(s) -
Yan Guoyi,
Hou Manzhou,
Luo Jiang,
Pu Chunlan,
Hou Xueyan,
Lan Suke,
Li Rui
Publication year - 2018
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13109
Subject(s) - pharmacophore , virtual screening , hela , docking (animal) , chemistry , computational biology , molecular dynamics , biochemistry , cell , biology , medicine , computational chemistry , nursing
Bromodomain is a recognition module in the signal transduction of acetylated histone. BRD 4, one of the bromodomain members, is emerging as an attractive therapeutic target for several types of cancer. Therefore, in this study, an attempt has been made to screen compounds from an integrated database containing 5.5 million compounds for BRD 4 inhibitors using pharmacophore‐based virtual screening, molecular docking, and molecular dynamics simulations. As a result, two molecules of twelve hits were found to be active in bioactivity tests. Among the molecules, compound 5 exhibited potent anticancer activity, and the IC 50 values against human cancer cell lines MV 4‐11, A375, and HeLa were 4.2, 7.1, and 11.6 μ m , respectively. After that, colony formation assay, cell cycle, apoptosis analysis, wound‐healing migration assay, and Western blotting were carried out to learn the bioactivity of compound 5 .