Discovery of novel human acrosin inhibitors by virtual screening |
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Authors: | Xuefei Liu Guoqiang Dong Jue Zhang Jingjing Qi Canhui Zheng Youjun Zhou Ju Zhu Chunquan Sheng Jiaguo Lü |
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Institution: | (1) School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, People’s Republic of China; |
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Abstract: | Human acrosin is an attractive target for the discovery of male contraceptive drugs. For the first time, structure-based drug
design was applied to discover structurally diverse human acrosin inhibitors. A parallel virtual screening strategy in combination
with pharmacophore-based and docking-based techniques was used to screen the SPECS database. From 16 compounds selected by
virtual screening, a total of 10 compounds were found to be human acrosin inhibitors. Compound 2 was found to be the most potent hit (IC50 = 14 μM) and its binding mode was investigated by molecular dynamics simulations. The hit interacted with human acrosin mainly
through hydrophobic and hydrogen-bonding interactions, which provided a good starting structure for further optimization studies. |
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