Designing novel quercetin derivatives as matrix metalloproteinase-9 inhibitors in colon carcinoma: An In vitro and in silico approach

• Main Authors: Sangeeta Ballav, Kiran Bharat Lokhande, Ipshita Dabhi, Sonal Inje, Amit Ranjan, K Venkateswara Swamy, Soumya Basu
• Format: Article
• Language: English
• Published: Wolters Kluwer Medknow Publications 2020-01-01
• Series: Journal of Dental Research and Review
• Subjects: colon cancer; matrix metalloproteinase-9; molecular docking; molecular dynamic simulation; quercetin
• Online Access: http://www.jdrr.org/article.asp?issn=2348-2915;year=2020;volume=7;issue=5;spage=30;epage=35;aulast=Ballav

Background: Matrix metalloproteinase-9 (MMP-9) plays an important role in activating several signaling molecules and pathways during inflammation, wound healing, and cancer progression. Since flavonoids have been shown to exhibit anti-inflammatory properties, we assessed the antiproliferative activity of quercetin, a flavonoid on colon carcinoma cell line through in vitro assays, and in order to design more specific MMP-9 inhibitors, we have used insilico approach to obtain potent quercetin derivatives. Materials and Methods: The aim of the present study was to investigate the effect of quercetin on cell viability and migration on cultured HCT-15 cells using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay and wound healing assay. The docking analysis of quercetin and its derivatives with the crystal structure of MMP-9 (PDB ID: 3OE9) was performed using FlexX software. Result: Quercetin showed an antiproliferative and antimigratory activity on HCT-15 cells in time- and dose-dependent manner. Conclusion: Novel quercetin derivatives targeting MMP-9 have been identified for further synthesis and validation.