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3D-QSAR studies and molecular docking on [5-(4-amino-1H-benzoimidazol-2-yl)-furan-2-yl]-phosphonic acid derivatives as fructose-1,6-biphophatase inhibitors

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Abstract

Fructose-1,6-biphophatase has been regarded as a novel therapeutic target for the treatment of type 2 diabetes mellitus (T2DM). 3D-QSAR and docking studies were performed on a series of [5-(4-amino-1H-benzoimidazol-2-yl)-furan-2-yl]-phosphonic acid derivatives as fructose-1,6-biphophatase inhibitors. The CoMFA and CoMSIA models using thirty-seven molecules in the training set gave r 2cv values of 0.614 and 0.598, r 2 values of 0.950 and 0.928, respectively. The external validation indicated that our CoMFA and CoMSIA models possessed high predictive powers with r 20 values of 0.994 and 0.994, r 2m values of 0.751 and 0.690, respectively. Molecular docking studies revealed that a phosphonic group was essential for binding to the receptor, and some key features were also identified. A set of forty new analogues were designed by utilizing the results revealed in the present study, and were predicted with significantly improved potencies in the developed models. The findings can be quite useful to aid the designing of new fructose-1,6-biphophatase inhibitors with improved biological response.

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Acknowledgments

This research work is supported by “the Fundamental Research Funds for the Central Universities” (No. 21610405), China.

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Authors and Affiliations

  1. Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, 510632, Guangzhou, People’s Republic of China

    Ping Lan, Mei-Qi Xie, Yue-Mei Yao, Wan-Na Chen & Wei-Min Chen

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  1. Ping Lan
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  2. Mei-Qi Xie
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Correspondence to Wei-Min Chen.

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Lan, P., Xie, MQ., Yao, YM. et al. 3D-QSAR studies and molecular docking on [5-(4-amino-1H-benzoimidazol-2-yl)-furan-2-yl]-phosphonic acid derivatives as fructose-1,6-biphophatase inhibitors. J Comput Aided Mol Des 24, 993–1008 (2010). https://doi.org/10.1007/s10822-010-9391-z

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  • DOI: https://doi.org/10.1007/s10822-010-9391-z

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