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Comparative molecular similarity indices analysis for predicting anti-HIV activity of phenyl ethyl thiourea (PET) derivatives

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Abstract

Human immunodeficiency virus type-1 (HIV-1) is a pathogenic retrovirus and the causative agent of acquired immunodeficiency syndrome (AIDS). HIV-1 RT is one of the key enzymes in the duplication of HIV-1. Inhibitors of HIV-1 RT are classified as nonnucleoside reverse transcriptase inhibitors (NNRTIs) and NRTIs. NNRTIs bind in a region not associated with the active site of the enzyme. Within the NNRTIs category, there is a set of inhibitors commonly referred to as phenyl or pyridyl ethyl thiourea (PET) derivatives. The present three-dimensional (3D) quantitative structure–activity relationship (QSAR) study attempts to explore the structural requirements of (phenyl ethyl thiourea) PET derivatives for anti-HIV activity. Based on the structures and biodata of previous PET analogs, comparative molecular similarity indices analysis (CoMSIA) is performed to explain the structural requirements for the anti-HIV activity of PET derivatives. The CoMSIA studies resulted in reliable computational models. The obtained CoMSIA model has high predictive ability, q 2 = 0.584, r 2 = 0.882 and standard error of estimation (SEE) = 0.352, explaining the majority of the variance in the data with four partial least square (PLS) components. The predictive ability of the developed models (3D QSAR) was also confirmed by using a test (external validation) set comprised of 11 molecules with a predicted r 2 value of 0.871. It is shown that the steric, electrostatic, hydrophobic, and hydrogen-bond acceptor and donor properties predicted by CoMSIA contours can be related to anti-HIV activity. This model is a significant guide to trace the features that really matter especially with respect to the design of novel compounds.

Graphical Abstract

Comparative molecular similarity indices analysis for predicting anti-HIV activity of phenyl ethyl thiourea (PET) derivatives

The parameters indicated in the substitution position of compound are responsible for anti-HIV activity.

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Acknowledgements

We would like to thank Prof. B. Suresh, Principal, J.S.S. College of Pharmacy, Ooty (TN), India for providing access to the computational resources. One of the authors V. Ravichandran is thankful to AICTE, New Delhi, for providing fellowship.

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Authors and Affiliations

  1. Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Vishwavidyalaya, Sagar, (M.P), 470 003, India

    Veerasamy Ravichandran & Ram Kishore Agrawal

  2. Department of Pharmaceutical Chemistry, J. S. S. College of Pharmacy, Ooty, (TN), India

    Bommenahath Ravanappa Prashantha Kumar & Sundaram Sankar

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  1. Veerasamy Ravichandran
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  2. Bommenahath Ravanappa Prashantha Kumar
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  3. Sundaram Sankar
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  4. Ram Kishore Agrawal
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Correspondence to Veerasamy Ravichandran.

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Ravichandran, V., Kumar, B.R.P., Sankar, S. et al. Comparative molecular similarity indices analysis for predicting anti-HIV activity of phenyl ethyl thiourea (PET) derivatives. Med Chem Res 17, 1–11 (2008). https://doi.org/10.1007/s00044-007-9087-7

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  • DOI: https://doi.org/10.1007/s00044-007-9087-7

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