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3D-QSAR and docking studies of 3-arylquinazolinethione derivatives as selective estrogen receptor modulators

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Abstract

3D-QSAR and molecular docking analysis were performed to explore the interaction of estrogen receptors (ERα and ERβ) with a series of 3-arylquinazolinethione derivatives. Using the conformations of these compounds revealed by molecular docking, CoMFA analysis resulted in the first quantitative structure-activity relationship (QSAR) and first quantitative structure-selectivity relationship (QSSR) models predicting the inhibitory activity against ERβ and the selectivity against ERá. The q2 and R2 values, along with further testing, indicate that the obtained 3D-QSAR and 3D-QSSR models will be valuable in predicting both the inhibitory activity and selectivity of 3-arylquinazolinethione derivatives for these protein targets. A set of 3D contour plots drawn based on the 3D-QSAR and 3D-QSSR models reveal modifications of substituents at C2 and C5 of the quinazoline which my be useful to improve both the activity and selectivity of ERβ/ ERα. Results showed that both the steric and electrostatic factors should appropriately be taken into account in future rational design and development of more active and more selective ERβ inhibitors for the therapeutic treatment of osteoporosis.

Structures of ERβ binding with compounds 1aar, 1ax and 1aag obtained from molecular docking

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Acknowledgements

This work is supported by the Scientific Research Common Program of Beijing Municipal Commission of Education. The authors are grateful to the kind help of Dr. Yuandong Hu and Miss Mei Zhou, Beijing Hongcam Software Technologies Co. Ltd.

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Authors and Affiliations

  1. Department of Chemistry, Capital Normal University, Beijing, 100037, People’s Republic of China

    Aijing Xiao, Zhuoyong Zhang, Liying An & Yuhong Xiang

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  1. Aijing Xiao
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  2. Zhuoyong Zhang
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  3. Liying An
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  4. Yuhong Xiang
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Correspondence to Zhuoyong Zhang.

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Xiao, A., Zhang, Z., An, L. et al. 3D-QSAR and docking studies of 3-arylquinazolinethione derivatives as selective estrogen receptor modulators. J Mol Model 14, 149–159 (2008). https://doi.org/10.1007/s00894-007-0264-x

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  • DOI: https://doi.org/10.1007/s00894-007-0264-x

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