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3D-QSAR and docking studies on pyridopyrazinones as BRAF inhibitors

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Abstract

BRAF has become an important and exciting therapeutic target toward human cancer. 3D-QSAR and docking studies were performed to explore the interaction of the BRAF with a series of pyridopyrazinones. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods were carried out in terms of their potential for predictability. The CoMFA and CoMSIA models using 71 compounds in the training set gave r 2cv values of 0.567 and 0.662, r 2 values of 0.900 and 0.907, respectively. The 3D contour maps generated by the CoMFA and CoMSIA models were used to identify the key structural requirements responsible for the biological activity. Molecular docking was applied to explore the binding mode between the ligands and the receptor. The information obtained by 3D-QSAR models may be useful to design novel potential BRAF inhibitors.

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Acknowledgments

The project was supported by the Special Item Fund of Central University Basic Scientific Research Operation Fee in South-Central University for Nationalities (FJ Song Group).

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Authors and Affiliations

  1. College of Pharmacy, South Central University for Nationalities, 708 Minyuan Road, Wuhan, 430074, People’s Republic of China

    Yong Ai, Shao-Teng Wang & Chu Tang

  2. College of Life Sciences/Key Laboratory for Biotechnology of the State Ethnic Affairs Commission, South Central University for Nationalities, 708 Minyuan Road, Wuhan, 430074, People’s Republic of China

    Fa-Jun Song

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

    Ping-Hua Sun

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  1. Yong Ai
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  2. Shao-Teng Wang
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  3. Chu Tang
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  4. Ping-Hua Sun
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  5. Fa-Jun Song
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Correspondence to Ping-Hua Sun or Fa-Jun Song.

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Ai, Y., Wang, ST., Tang, C. et al. 3D-QSAR and docking studies on pyridopyrazinones as BRAF inhibitors. Med Chem Res 20, 1298–1317 (2011). https://doi.org/10.1007/s00044-010-9468-1

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  • DOI: https://doi.org/10.1007/s00044-010-9468-1

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