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Molecular docking studies of chromone derivatives against wild type and mutant strains of HIV-1 protease

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Abstract

Developing a new HIV-1 protease (HIV-1 PR) inhibitor is still a challenging task to overcome the drug resistance mutations in the HIV-PR. In this study, docking simulations of chromone derivatives against wild type and eleven mutant variants HIV-1 PR were investigated using GOLD and Autodock programs. From both GOLD and Autodock results, chromone 3, the experimentally observed highly potent HIV-1 PR inhibitor, showed stronger binding affinity against every studied mutant strain (2AVS, 2AVO, 2AVV, 1MES, 1MET, 1MEU, 1SDU, 1SDV, 1C6Y, 2F8O, and 1SH9) than the wild-type enzyme (1AJX). Chromone 32, another potent inhibitor as well as chromones 33, 34, 37, and 47 also showed high binding interaction with several mutant-type enzymes. The coherent picture of the interactions at the active sites of mutant PR should facilitate the further design and development of new potent inhibitor against multidrug-resistant virus.

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Acknowledgments

This project is supported by the Office of the High Education Commission and Mahidol University under the National Research Universities Initiative.

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Authors and Affiliations

  1. Faculty of Pharmacy, Srinakharinwirot University, Nakhon Nayok, 26120, Thailand

    Patcharawee Nunthanavanit

  2. Center of Excellence for Innovation in Drug Design and Discovery, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhya Road, Bangkok, 10400, Thailand

    Jiraporn Ungwitayatorn

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  1. Patcharawee Nunthanavanit
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  2. Jiraporn Ungwitayatorn
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Correspondence to Jiraporn Ungwitayatorn.

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Nunthanavanit, P., Ungwitayatorn, J. Molecular docking studies of chromone derivatives against wild type and mutant strains of HIV-1 protease. Med Chem Res 23, 4198–4208 (2014). https://doi.org/10.1007/s00044-014-0992-2

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  • DOI: https://doi.org/10.1007/s00044-014-0992-2

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