Abstract
Indolylarylsulfones (IASs) have received considerable interest during the last decades due to high potency against HIV-1 as non-nucleoside reverse transcriptase inhibitors. In present work, quantitative structure–activity relationship (QSAR) and molecular docking analyses were performed to model the anti-HIV-1 activity of 36 IASs. 2D and 3D-descriptors, genetic algorithm, internal and external validations were used to develop statistically robust four-parametric QSAR models. The best QSAR model is with R 2tr = 0.8608. The QSAR analysis reveals that the activity of IASs depends on the presence of electronegative and heavy atoms at the internal atmosphere of the compounds. The docking analysis reveals that lipophilic and H-bonding interactions are the prominent interactions among IASs and the receptor. The QSAR analysis proved to be a useful tool in the prediction of anti-HIV-1 activity of congeneric compounds and some important insights were also found that will be useful to guide for the synthesis of new IASs with improved activity.
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Abbreviations
- QSAR:
-
Quantitative structure–activity relationship
- NNRTIs:
-
Non-nucleoside reverse transcriptase inhibitors
- IASs:
-
Indolylarylsulfones
- WHO:
-
World Health Organization
- AIDS:
-
Acquired Immunodeficiency Syndrome
- HAART:
-
Highly active antiretroviral therapy
- RT:
-
Reverse transcriptase
- GA:
-
Genetic algorithm
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Acknowledgments
We are thankful to Dr. K. N. Patil, Amravati and Dr. Ashraf Ali, Singapore for useful discussions. Sincere thanks to Dr. F. C. Raghuwanshi for encouragement and facilities.
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Masand, V.H., Mahajan, D.T., Hadda, T.B. et al. Molecular docking and quantitative structure–activity relationship (QSAR) analyses of indolylarylsulfones as HIV-1 non-nucleoside reverse transcriptase inhibitors. Med Chem Res 23, 417–425 (2014). https://doi.org/10.1007/s00044-013-0647-8
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DOI: https://doi.org/10.1007/s00044-013-0647-8