Molecular Docking and Inhibition of Matrix Metalloproteinase-2 by Novel Difluorinatedbenzylidene Curcumin Analog

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2015 Apr 23

PMID 25901198

Citations 16

Authors

Aamir Ahmad

Afreen Sayed

Kevin R Ginnebaugh

Vivek Sharma

Anita Suri

Arundhati Saraph

Subhash Padhye

Fazlul H Sarkar

Affiliations

Soon will be listed here.

Abstract

We recently described the synthesis and characterization of a novel difluorinatedbenzylidene analog of curcumin, commonly referred as CDF, which demonstrated significantly enhanced bioavailability and in vivo anticancer activity. CDF targets many factors similar to curcumin, albeit with more potency, as reported previously. To further highlight this differential behavior of CDF, we chose matrix metalloproteinase protein MMP-2 which is involved in the processes of invasion and metastasis of human tumors. Both curcumin and CDF were characterized for their binding characteristics using in silico docking studies; they were also evaluated via biological assays involving gelatin zymography, miRNA analysis, invasion assays and ELISA. CDF was found to inhibit MMP-2 expression and activity in A549 and H1299 NSCLC cells much more effectively than curcumin, validating molecular modeling results. miR-874, an MMP-2-targeting miRNA, was up-regulated by CDF. Thus, it appears that CDF can inhibit MMP-2 through multiple mechanisms. Our results are suggestive of a more potent inhibition of invasion and metastasis by CDF, compared to curcumin, thus warranting its further evaluation as an effective anticancer agent.

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