Compounds isolated from Ageratum houstonianum inhibit the activity of matrix metalloproteinases (MMP-2 and MMP-9): An oncoinformatics study

Anupriya Verma; Syed Mohd Danish Rizvi; Sibhghatulla Shaikh; Mohd Afaque Ansari; Shazi Shakil; Fauzia Ghazal; Mohd Haris Siddiqui; Mohd Haneef; Ajijur Rehman

Articles

Abstract

Pharmacognosy Magazine,2014,10,37,18-26.

DOI:10.4103/0973-1296.126653

Published:February 2014

Type:Original Article

Authors:

Author(s) affiliations:

Anupriya Verma¹, Syed Mohd Danish Rizvi², Sibhghatulla Shaikh², Mohd Afaque Ansari², Shazi Shakil¹, Fauzia Ghazal², Mohd Haris Siddiqui¹, Mohd Haneef¹, Ajijur Rehman²
¹ Department of Bio-Engineering, Integral University, Lucknow, Uttar Pradesh, India
² Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India

Abstract:

Background: In osteosarcoma tissue, both MMP-2 and MMP-9 are over expressed compared to their expression in non-affected stromal tissue. Hence, gelatinases are attractive targets for anti-osteosarcoma drugs. Objective: To study the inhibitory activity of compounds isolated from Ageratum houstonianum against MMP-2 and MMP-9 by in-silico approach. Material and Methods: We performed docking study using 'Autodock 4.2' between 1,2-benzenedicarboxylic acid-bis (2-ethylhexyl) ester; squalene; 3,5-bis (1,1-dimethylethyl) phenol; pentamethyl tetrahydro-5H-chromene; (1, 4-cyclohexylphenyl) ethanone and 6-vinyl-7-methoxy-2,2-dimethylchromene with MMP-2 and MMP-9. Results: Among all six compounds isolated from Ageratum houstonianum, (1, 4-cyclohexylphenyl) ethanone showed the maximum potential as a putative inhibitor of both MMP-2 and MMP-9 enzymes with reference to ΔG (−7.95 and −8.2 kcal/mol, respectively) and Ki (1.48 and 0.98 μM, respectively) values. Total intermolecular energy of docking for (1, 4-cyclohexylphenyl) ethanone-MMP catalytic domain-interaction was found to be −8.55 kcal/mol for MMP-2 and −9.21 kcal/mol for MMP-9. Conclusion: This study explores molecular interactions between human MMPs (MMP-2 and MMP-9) and six natural compounds. This study predicts that (1,4-cyclohexylphenyl) ethanone is a more efficient inhibitor of human MMP-2 and MMP-9 enzymes compared to the other natural compounds used in this study with reference to Ki and ΔG values.