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Discovery of novel human acrosin inhibitors by virtual screening

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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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Authors and Affiliations

  1. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, People’s Republic of China

    Xuefei Liu, Guoqiang Dong, Jue Zhang, Jingjing Qi, Canhui Zheng, Youjun Zhou, Ju Zhu, Chunquan Sheng & Jiaguo Lü

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  1. Xuefei Liu
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  2. Guoqiang Dong
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  3. Jue Zhang
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  4. Jingjing Qi
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  5. Canhui Zheng
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  6. Youjun Zhou
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  7. Ju Zhu
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  8. Chunquan Sheng
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  9. Jiaguo Lü
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Correspondence to Chunquan Sheng or Jiaguo Lü.

Electronic supplementary material

Below is the link to the electronic supplementary material.

10822_2011_9476_MOESM1_ESM.pdf

Dataset used in virtual screening test; Binding mode of hit 2 with ram and boar acrosin. Supplementary material 1 (PDF 401 kb)

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Liu, X., Dong, G., Zhang, J. et al. Discovery of novel human acrosin inhibitors by virtual screening. J Comput Aided Mol Des 25, 977–985 (2011). https://doi.org/10.1007/s10822-011-9476-3

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  • DOI: https://doi.org/10.1007/s10822-011-9476-3

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