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Identification of CYP3A4 inhibitors as potential anti-cancer agents using pharmacoinformatics approach

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Abstract

Biguanide derivatives exhibit a wide variety of therapeutic applications, including anti-cancer effects. Metformin is an effective anti-cancer agent against breast cancer, lung cancer, and prostate cancer. In the crystal structure (PDB ID: 5G5J), it was found that metformin is found in the active site of CYP3A4, and the associated anti-cancer effect was explored. Taking clues from this work, pharmacoinformatics research has been carried out on a series of known and virtual biguanide, guanylthiourea (GTU), and nitreone derivatives. This exercise led to the identification of more than 100 species that exhibit greater binding affinity toward CYP3A4 in comparison to that of metformin. Selected six molecules were subjected to molecular dynamics simulations, and the results are presented in this work.

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Funding

Department of Biotechnology, Government of India for financial support (grant number: BT/PR140164); SERB, Department of Science and Technology, Government of India for funding (PDF/2020/002825).

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  1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar-160062, Punjab, India

    Pravin J. Wanjari, Asutosh Rath, Rohit Y. Sathe & Prasad V. Bharatam

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Pravin J. Wanjari: revised the manuscript critically and wrote the manuscript, Asutosh Rath: execution of idea, Rohit Y. Sathe: revised the manuscript critically, and Prasad V. Bharatam: generation of idea, analysis, and revised it critically.

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Correspondence to Prasad V. Bharatam.

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Wanjari, P.J., Rath, A., Sathe, R.Y. et al. Identification of CYP3A4 inhibitors as potential anti-cancer agents using pharmacoinformatics approach. J Mol Model 29, 156 (2023). https://doi.org/10.1007/s00894-023-05538-z

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