3D-QSAR, DOCKING STUDY, PHARMACOPHORE MODELING AND ADMET PREDICTION OF 2-AMINO-PYRAZOLOPYRIDINE DERIVATIVES AS POLO-LIKE KINASE 1 INHIBITORS


Jaiprakash Sangshetti, Firoz A. Kalam Khan, Yasar Q. Qazi, Manoj G. Damale, Zahid Zaheer

Abstract


Objective: The polo-like kinase 1 (plk1) plays important roles in the regulation of mitotic progression, including mitotic entry, spindle formation, chromosome segregation and cytokinesis. Thus, plk1 is considered as a good target for chemotherapeutic intervention. The main objectives of this research were to in silico screen the 2-amino-pyrazolopyridine derivatives as plk1 inhibitors and develop pharmacophore for enhanced activity.

Methods: The three-dimensional quantitative structure–activity relationship (3D-QSAR), docking and pharmacophore identification studies on 2-amino-pyrazolopyridine derivatives as plk1 inhibitors have been carried out using V Life MDS 4.3 software. The stepwise 3D-QSAR kNN-MFA method was applied to derive QSAR model. Also, ADMET prediction was performed using FAF Drugs 2 which runs on Linux OS.

Results: The information rendered by 3D-QSAR models may lead to a better understanding and designing of novel plk1 inhibitor molecules. The molecular docking analysis was carried out to better understand the interactions between plk1 enzyme and inhibitors in this series. Hydrophobic and hydrogen bond interactions lead to identification of active binding sites. The results of pharmacophore studies showed that hydrogen bond accepters, aromatic and aliphatic centers are the important features for polo-like kinase 1 inhibitor activity. ADMET prediction of these compounds showed good drug like properties.

Conclusion: The combination of the 3D-QSAR, docking, pharmacophore modeling and ADMET prediction is an important tool in understanding the structural requirements for design of novel, potent and selective plk1 inhibitors and can be employed to design new  drug discovery and can be used for derivatives of 2-amino-pyrazolopyridines with specific plk1 inhibitory activity.

 


Keywords


Polo-like kinase 1 inhibitors, 3D-QSAR, kNN-MFA model, Docking study, Pharmacophore modeling, ADMET properties.

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About this article

Title

3D-QSAR, DOCKING STUDY, PHARMACOPHORE MODELING AND ADMET PREDICTION OF 2-AMINO-PYRAZOLOPYRIDINE DERIVATIVES AS POLO-LIKE KINASE 1 INHIBITORS

Keywords

Polo-like kinase 1 inhibitors, 3D-QSAR, kNN-MFA model, Docking study, Pharmacophore modeling, ADMET properties.

Date

01-09-2014

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 6, Issue 8, 2014 Page: 217-223

Online ISSN

0975-1491

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470 Views | 93 Downloads

Authors & Affiliations

Jaiprakash Sangshetti
Associate Professor Y.B.Chavan College of Pharmacy Aurangabad-431001(MS) INDIA
India

Firoz A. Kalam Khan
Rafiq Zakaria Campus, Y.B. Chavan College of Pharmacy, Aurangabad 431001 (MS) India
India

Yasar Q. Qazi
Rafiq Zakaria Campus, Y.B. Chavan College of Pharmacy, Aurangabad 431001 (MS) India
India

Manoj G. Damale
2MGM’s Institute of Biosciences and Technology, Aurangabad 431003 (MS) India.
India

Zahid Zaheer
Rafiq Zakaria Campus, Y.B. Chavan College of Pharmacy, Aurangabad 431001 (MS) India
India


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