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

Tanwar, Omprakash, Deora, Girdhar Singh, Tanwar, Lalima, Kumar, Gautam, Janardhan, Sridhara, Alam, Md. Mumtaz, Shaquiquzzaman, Md. and Akhter, Mymoona (2014) Novel hydrazine derivatives as selective DPP-IV inhibitors: findings from virtual screening and validation through molecular dynamics simulations. Journal of Molecular Modeling, 20 4: 2118.1-2118.16. doi:10.1007/s00894-014-2118-7


Author Tanwar, Omprakash
Deora, Girdhar Singh
Tanwar, Lalima
Kumar, Gautam
Janardhan, Sridhara
Alam, Md. Mumtaz
Shaquiquzzaman, Md.
Akhter, Mymoona
Title Novel hydrazine derivatives as selective DPP-IV inhibitors: findings from virtual screening and validation through molecular dynamics simulations
Journal name Journal of Molecular Modeling   Check publisher's open access policy
ISSN 1610-2940
0948-5023
Publication date 2014-01-01
Sub-type Article (original research)
DOI 10.1007/s00894-014-2118-7
Open Access Status Not Open Access
Volume 20
Issue 4
Start page 2118.1
End page 2118.16
Total pages 16
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
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-IVas 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.
Keyword Dipeptidyl peptidase-IV inhibitor
Hydrazine derivative
Molecular dynamics
Sitagliptine
Virtual screening
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Pharmacy Publications
 
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