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Modification and biological evaluation of novel 4-hydroxy-pyrone derivatives as non-peptidic HIV-1 protease inhibitors

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Abstract

In this study, we have modified 4-hydroxy-pyran-2-ones, especially introduced heteroatoms (S or O) into the substituents, and detected their interactions with the binding pockets of HIV-1 protease (PR). The results indicated that the ethoxyl groups at C-2′ and C-5′ of the phenyl ring could enhance the affinities to the S 1 ′ and S 2 ′ pockets and improve the inhibitory activities. The most potent compound 10f with an IC50 of 3.5 nM in enzymatic assay also exhibited good antiviral activity at the cellular level; it exhibited an EC50 value of 2.9 μM in Simian immunodeficiency virus-infected CEM cells and suppressed the PR activity in 293T cells using western blot analysis.

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Acknowledgment

This study was supported by the National Science Foundation of China (No. 30670415).

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Authors and Affiliations

  1. State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, No. 38, Haidian District, Beijing, People’s Republic of China

    Meizi He, Ning Yang, Chunlai Sun & Ming Yang

  2. Laboratory of Molecular Human Retrovirology, Department of Medical Microbiology, University of Manitoba, 508-745 William Avenue, Winnipeg, MB, R3E OJ9, Canada

    Xiaojian Yao

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  1. Meizi He
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  2. Ning Yang
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  3. Chunlai Sun
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  4. Xiaojian Yao
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  5. Ming Yang
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Correspondence to Ming Yang.

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He, M., Yang, N., Sun, C. et al. Modification and biological evaluation of novel 4-hydroxy-pyrone derivatives as non-peptidic HIV-1 protease inhibitors. Med Chem Res 20, 200–209 (2011). https://doi.org/10.1007/s00044-010-9307-4

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  • DOI: https://doi.org/10.1007/s00044-010-9307-4

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