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Developing 2D-QSAR models for naphthyridine derivatives against HIV-1 integrase activity

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Abstract

HIV-1 integrase is an extremely important nominee in developing new and effective drugs especially naphthyridine compounds against acquired immune deficiency syndrome. The quantitative structure–activity relationship (QSAR) modeling is the most powerful method in computer-aided drug design and will be used to help the design of new naphthyridine derivatives. Different computational 2D-QSAR procedures applied to predict the relationship between the computational descriptors of naphthyridine derivatives with their HIV-1 integrase inhibition activities. Four different models including stepwise-MLR, consensus stepwise-MLR, GAPLS-MLR, and consensus GAPLS-MLR with appropriate correlation between the calculated and experimental biological activities (pIC50) against HIV-1 integrase were generated. Predictive QSAR models were obtained with R 2training values of 0.848, 0.862, 0.709, and 0.751 as well as R 2test values of 0.521, 0.651, 0.502, and 0.775 for stepwise-MLR, consensus stepwise-MLR, GAPLS-MLR, and consensus GAPLS-MLR models, respectively. QSAR models are high efficiency in prediction of the pIC50 in comparison with other models because of concerning the combination of “quantum and molecular mechanical” descriptors. Combination of “quantum” and “molecular mechanical” descriptors improved our models with high efficient test set activity prediction potency. The obtained results provided useful information for understanding the effects of polarizability, electronegativity, and especially functional groups such as aromatic nitrogens that are important for the activities of naphthyridine compounds. The developed QSAR models will be efficient for the rational design of potent naphthyridine derivatives against HIV-1 integrase activity.

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Acknowledgments

The authors would like to thank the Iran National Science Foundation (INSF) and the Research Institute for Fundamental Sciences (RIFS)-University of Tabriz for their financial supports.

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Authors and Affiliations

  1. Research Institute for Fundamental Sciences (RIFS), University of Tabriz, Tabriz, Iran

    Mostafa Zakariazadeh & Abolfazl Barzegar

  2. Department of Biochemistry, Science and Research Branch, Islamic Azad University, Kurdistan, Iran

    Mostafa Zakariazadeh

  3. The School of Advanced Biomedical Sciences (SABS), Tabriz University of Medical Sciences, Tabriz, Iran

    Abolfazl Barzegar

  4. Drug Applied Research Center and Pharmacy Faculty, Tabriz University of Medical Sciences, Tabriz, Iran

    Somaieh Soltani

  5. Department of Biology, Faculty of Science, Golestan University, Gorgan, Iran

    Hassan Aryapour

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  1. Mostafa Zakariazadeh
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  2. Abolfazl Barzegar
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  3. Somaieh Soltani
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  4. Hassan Aryapour
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Correspondence to Abolfazl Barzegar.

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Zakariazadeh, M., Barzegar, A., Soltani, S. et al. Developing 2D-QSAR models for naphthyridine derivatives against HIV-1 integrase activity. Med Chem Res 24, 2485–2504 (2015). https://doi.org/10.1007/s00044-014-1305-5

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  • DOI: https://doi.org/10.1007/s00044-014-1305-5

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