3D-QSAR AND MOLECULAR DOCKING STUDIES ON 1, 2, 4 TRIAZOLES AS MetAP2 INHIBITORS


Stephen Philip, Bharatkumar Inturi, Bhavya K, Gurubasavaraj V Pujar, Madhusudan Purohit

Abstract


Objective: Angiogenesis inhibitors are a novel class of promising therapeutic agents for treating cancer and other human diseases. Biological transformations and pathways that play a role in angiogenesis are, therefore, particularly attractive targets as potential methods for inhibiting solid tumors. MetAP2 is of particular interest because the enzyme plays a key role in angiogenesis, the growth of new blood vessels, which is necessary for the progression of diseases including solid tumor cancers and rheumatoid arthritis. In this paper we report the quantitative structure activity relationship and docking studies of 1, 2, 4 triazole derivatives for designing novel MetAP2 inhibitors.

Methods: Tripos Sybyl X 2.1 program was used to conduct docking based CoMFA, CoMSIA and Topomer CoMFA QSAR modeling for a dataset of 77 triazoles.

Results: The CoMFA, CoMSIA and Topomer CoMFA models demonstrated good statistical results with cross-validated coefficient (q2) of 0.703, 0.704, 0.746 and correlation coefficient (r2) of 0.894, 0.889, 0.886 respectively and these models have been externally validated.

Conclusion: Based on the statistical results obtained from the above model, the CoMFA, CoMSIA and Topomer CoMFA model can be utilized to design new molecules having 1, 2, 4 triazoles as common core with significant MetAP2 inhibitory activity.

 


Keywords


QSAR, CoMFA, CoMSIA, 1,2,4-triazole, MetAP2.

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About this article

Title

3D-QSAR AND MOLECULAR DOCKING STUDIES ON 1, 2, 4 TRIAZOLES AS MetAP2 INHIBITORS

Keywords

QSAR, CoMFA, CoMSIA, 1,2,4-triazole, MetAP2.

Date

01-10-2014

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 6, Issue 9, 2014 Page: 205-212

Online ISSN

0975-1491

Statistics

203 Views | 93 Downloads

Authors & Affiliations

Stephen Philip
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS University, Mysore 570015, India.
India

Bharatkumar Inturi
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS University, Mysore 570015, India.
India

Bhavya K
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS University, Mysore 570015, India.
India

Gurubasavaraj V Pujar
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS University, Mysore 570015, India.
India

Madhusudan Purohit
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS University, Mysore 570015, India.
India


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