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Pharmacophore modeling of some novel indole β-diketo acid and coumarin-based derivatives as HIV integrase inhibitors

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Abstract

To design new chemotypes with enhanced potencies against the HIV integrase enzyme, 3D pharmacophore models were generated and QSAR study was carried out on 44 novel indole β-diketo acid derivatives and coumarin-based Inhibitors. A five-point pharmacophore with two hydrogen bond acceptors (A) and three aromatic rings (R) as pharmacophore features was developed by PHASE module of Schrodinger suite. The pharmacophore hypothesis yielded a statistically significant 3D-QSAR model, with a correlation coefficient of R 2 = 0.81 for training set compounds. The model generated showed excellent predictive power, with a correlation coefficient of Q 2 = 0.69 for a randomly chosen test set of eight compounds. The 3D-QSAR plots illustrated insights into the structure activity relationship of these compounds which may helps in the design and development of novel integrase inhibitors.

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Acknowledgments

LVS gratefully acknowledge “Department of Science and Technology, Govt. of India” for awarding Young Scientist Fellowship (SR/FT/LS-161/2008). Authors like to acknowledge Principal of the institute for providing facilities to carryout the work.

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Authors and Affiliations

  1. Drug Design and Development, R. C. Patel Institute of Pharmaceutical Education and Research, Dhule District, Shirpur, Maharashtra, 425405, India

    Shailesh V. Jain & Lalit V. Sonawane

  2. Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Dhule District, Shirpur, Maharashtra, 425405, India

    Ravindra R. Patil & Sanjaykumar B. Bari

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  1. Shailesh V. Jain
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  2. Lalit V. Sonawane
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  3. Ravindra R. Patil
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  4. Sanjaykumar B. Bari
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Correspondence to Shailesh V. Jain.

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Jain, S.V., Sonawane, L.V., Patil, R.R. et al. Pharmacophore modeling of some novel indole β-diketo acid and coumarin-based derivatives as HIV integrase inhibitors. Med Chem Res 21, 165–173 (2012). https://doi.org/10.1007/s00044-010-9520-1

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  • DOI: https://doi.org/10.1007/s00044-010-9520-1

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