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Molecular docking studies on tetrahydroimidazo-[4,5,1-jk][1,4]-benzodiazepinone (TIBO) derivatives as HIV-1 NNRT inhibitors

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Abstract

At present, chemotherapy seems to be the main weapon in the arsenal of remedies for the ongoing crusade against AIDS. The mode of binding of the TIBO family of inhibitors has been of interest because these compounds do not fit the two-hinged-ring model as generally observed in the NNRTIs. Flexible docking simulations were performed with a series of 53 TIBO derivatives as NNRTIs. Binding preferences as well as the structural and energetic factors associated with them were studied. A good correlation (r 2 = 0.849, q 2 = 0.843) was observed between the biological activity and binding affinity of the compounds which suggest that the identified binding conformations of these inhibitors are reliable. Further screening of PubChem database yielded novel scaffolds. Our studies suggest that modifications to the TIBO group of inhibitors might enhance their binding efficacy and hence, potentially, their therapeutic utility.

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Acknowledgement

The author wishes to acknowledge Dr. R. C. Saraswat, Director, S.G.S. I.T.S, Indore.

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Authors and Affiliations

  1. Department of Applied Chemistry, Shri GS Institute of Technology and Sciences, 3/6 Manoramaganj, Indore, 452001, MP, India

    Nitin S. Sapre & Nilanjana Pancholi

  2. Department of Chemistry, Govt. P.G. College, MHOW, MP, India

    Swagata Gupta

  3. Department of Computer Science, SD Bansal College of Technology, Indore, MP, India

    Neelima Sapre

Authors
  1. Nitin S. Sapre
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  2. Swagata Gupta
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  3. Nilanjana Pancholi
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  4. Neelima Sapre
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Correspondence to Nitin S. Sapre.

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Sapre, N.S., Gupta, S., Pancholi, N. et al. Molecular docking studies on tetrahydroimidazo-[4,5,1-jk][1,4]-benzodiazepinone (TIBO) derivatives as HIV-1 NNRT inhibitors. J Comput Aided Mol Des 22, 69–80 (2008). https://doi.org/10.1007/s10822-007-9161-8

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  • DOI: https://doi.org/10.1007/s10822-007-9161-8

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