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QSAR Studies of Sulfonamide Hydroxamates Derivatives as MMP-2 Inhibitors Topomer CoMFA and Molecular Docking

[ Vol. 17 , Issue. 11 ]

Author(s):

Jian-Bo Tong*, Feng Yi, Ding Luo and Tian-Hao Wang   Pages 1364 - 1371 ( 8 )

Abstract:


Background: In recent years, cancer has become the main cause of death and it is a serious threat to human health, so the development of new, selective and safe anticancer drugs is still the focus of medical research. Matrix metalloproteinases-2 (MMP-2) has been determined to play an important role in the regulation of tumor angiogenesis, which is closely related to the development of the tumor. Therefore, MMP-2 is considered as a promising target for tumor therapy. In this study, Tomper comparative molecular field analysis (Topomer CoMFA) and molecular docking were used to investigate the important role of sulfonamide hydroxamate derivatives, an inhibitor of MMP-2, in the inhibition of angiogenesis.

Methods: Quantitative structure active relationship (QSAR) models of 35 sulfonamide hydroxamate derivatives with inhibitory MMPs were developed. The quantitative structure-activity relationship (QSAR) model was built by using Topomer comparative molecular field analysis (Topomer CoMFA) technique.

Results and Discussions: The results show that the cross-validated q2 value of the Topomer CoMFA model is 0.881 and the non-cross-validated r2 value is 0.967. The results show that the model is reasonable and reliable, and has good prediction ability. Molecular docking studies were used to find the actual conformations of chemicals in active sites of cancer protease, as well as the binding mode pattern to the binding site in MMP-2. The information provided by the 3D-QSAR model and molecular docking may lead to a better understanding of the structural requirements of 35 sulfonamide hydroxamate derivatives and help to design potential anti-cancer protease inhibitor molecules.

Conclusion: Thirty-five analogs were used in the 3D-QSAR study. Topomer CoMFA 3D-QSAR method was used to build the model, and the model was well predicted and statistically validated. The results of 3D-QSAR and molecular docking analysis provide theoretical guidance for the synthesis of new MMP-2 inhibitors.

Keywords:

Sulfonamide hydroxamate derivatives, MMP-2, 3D-QSAR, matrix metalloproteinases, topomer CoMFA, molecular docking.

Affiliation:

College of Chemistry and Chemical Engineering, Shaanxi University of Science and Technology, Xi'an 710021, College of Chemistry and Chemical Engineering, Shaanxi University of Science and Technology, Xi'an 710021, College of Chemistry and Chemical Engineering, Shaanxi University of Science and Technology, Xi'an 710021, College of Chemistry and Chemical Engineering, Shaanxi University of Science and Technology, Xi'an 710021



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