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


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.


CONCLUSIONS
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.
Department of Bio-Engineering, Integral University, Lucknow, Uttar Pradesh, India.
Anupriya
A
Verma
Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India.
Syed Mohd Danish
SM
Rizvi
Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India.
Sibhghatulla
S
Shaikh
Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India.
Mohd Afaque
MA
Ansari
Department of Bio-Engineering, Integral University, Lucknow, Uttar Pradesh, India.
Shazi
S
Shakil
Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India.
Fauzia
F
Ghazal
Department of Bio-Engineering, Integral University, Lucknow, Uttar Pradesh, India.
Mohd Haris
MH
Siddiqui
Department of Bio-Engineering, Integral University, Lucknow, Uttar Pradesh, India.
Mohd
M
Haneef
Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India.
Ajijur
A
Rehman
(1, 4-cyclohexylphenyl) ethanone; Ageratum houstonianum; docking; matrix metalloproteinase 2; matrix metalloproteinase 9; matrix metalloproteinases; oncoinformatics