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Topomer-CoMFA-based predictive modelling on 2,3-diaryl-substituted-1,3-thiazolidin-4-ones as non-nucleoside reverse transcriptase inhibitors

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Abstract

The reverse transcriptase enzyme has been identified as an attractive target to inhibit the HIV-1 proliferations. Studies about the structure activity relationship on a dataset of thiazolidin-4-ones were performed using the topomer-CoMFA. The obtained topomer-CoMFA model with steric and electrostatic field parameters based on two (labelled R1 and R2) fragments gave a statistically robust model (R 2 = 0.938; Q 2 = 0.719). The predictability of the developed model was assessed on a test set data with r 2pred  = 0.798. The results of topomer-CoMFA suggested that at R1 position, the large bulky groups at C-2 position with less electronegativity and small bulky groups with large electronegativity at C-6 position are favourable for bioactivity. The topomer-CoMFA results for electrostatic contour maps at R2 position, electron releasing groups at C-4, C-5 and C-6 position along with electronegative atoms at N1 and N3 of pyrimidine, N1 of pyridine or O1 of furan moiety, whereas steric contour maps favour the substitution of small bulky groups at the same position. Finally, the applicability domain of the model was defined on external dataset of thiazolidin-4-ones and the results further supported the reliability and robustness of topomer-CoMFA model, which could be further used for prediction of potential new thiazolidin-4-one analogues.

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Acknowledgments

The SK thankfully acknowledges the Council of Scientific and Industrial Research, New Delhi for financial support in the form of senior research fellowship. The authors are grateful to Director, Shri G.S. Institute of Technology and Science, Indore for providing the facility to carry out the work.

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  1. Computer-Aided Drug Design Lab, Department of Pharmacy, Shri Govindram Seksaria Institute of Technology and Science, 23, Park Road, Indore, 452003, M.P., India

    Surendra Kumar & Meena Tiwari

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  1. Surendra Kumar
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  2. Meena Tiwari
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Correspondence to Meena Tiwari.

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Kumar, S., Tiwari, M. Topomer-CoMFA-based predictive modelling on 2,3-diaryl-substituted-1,3-thiazolidin-4-ones as non-nucleoside reverse transcriptase inhibitors. Med Chem Res 24, 245–257 (2015). https://doi.org/10.1007/s00044-014-1105-y

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