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Novel hydrazine derivatives as selective DPP-IV inhibitors: findings from virtual screening and validation through molecular dynamics simulations

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Abstract

The present study demonstrates and validates the discovery of two novel hydrazine derivatives as selective dipeptidyl peptidase-IV (DPP-IV) inhibitors. Virtual screening (VS) of publicly available databases was performed using virtual screening workflow (VSW) of Schrödinger software against DPP-IV and the most promising hits were selected. Selectivity was further assessed by docking the hits against homology modeled structures of DPP8 and DPP9. Two novel hydrazine derivatives were selected for further studies based on their selectivity threshold. To assess their correct binding modes and stability of their complexes with enzyme, molecular dynamic (MD) simulation studies were performed against the DPP-IV protein and the results revealed that they had a better binding affinity towards DPP-IV as compared to DPP 8 and DPP 9. The binding poses were further validated by docking these ligands with different softwares (Glide and Gold). The proposed binding modes of hydrazines were found to be similar to sitagliptine and alogliptine. Thus, the study reveals the potential of hydrazine derivatives as highly selective DPP-IV inhibitors.

Structures of sitagliptine and the novel hydrazine identified by screening

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Acknowledgments

The authors wish to express their gratitude to Department of Science and Technology (DST), New Delhi (SERC/LS-295/2011) for providing financial assistance for the present study and Department of Biotechnology (DBT), New Delhi for providing Bioinformatics Infrastructure Facility.

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Authors and Affiliations

  1. Drug Design and Medicinal Chemistry Lab, Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Bioinformatics Infrastructure Facility (BIF), Jamia Hamdard, New Delhi, 110062, India

    Omprakash Tanwar, Gautam Kumar, Md. Mumtaz Alam, Md. Shaquiquzzaman & Mymoona Akhter

  2. Dr. Reddy’s Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad, 500046, India

    Girdhar Singh Deora

  3. The University of Queensland, School of Pharmacy, Brisbane, Qld, 4072, Australia

    Girdhar Singh Deora

  4. School of Biochemistry, Khandwa Road, DAVV, Indore, 452001, India

    Lalima Tanwar

  5. Raghavendra Institute of Pharmaceutical Education and Research (RIPER), Anantapur, 515721, Andhra Pradesh, India

    Sridhara Janardhan

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  1. Omprakash Tanwar
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Correspondence to Mymoona Akhter.

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Tanwar, O., Deora, G.S., Tanwar, L. et al. Novel hydrazine derivatives as selective DPP-IV inhibitors: findings from virtual screening and validation through molecular dynamics simulations. J Mol Model 20, 2118 (2014). https://doi.org/10.1007/s00894-014-2118-7

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