Interaction of Selected Terpenoids From Dalbergia sissoo With Catalytic Domain of Matrix Metalloproteinase-1: An In Silico Assessment of Their Anti-wrinkling Potential

Abstract

Matrix metalloproteinase-1 (MMP-1) is a predominant collagenase enzyme that cleaves collagen fibers, contributing to skin wrinkling. Matrix metalloproteinase-1 inhibitors of herbal origin may provide an earnest probability to offer a novel curative approach against MMP-1-mediated collagenolysis, prompted by ultraviolet (UV)-induced overexpression of MMP-1. In this in silico study, we have explored the MMP-1 inhibitory potential of selected terpenoids from Dalbergia sissoo extracts. Two triterpenoids (lupeol and betulin), 1 diterpenoid (phytol), and 1 ester derivative of lupeol (lupeol acetate) were studied along with a reference inhibitor (doxycycline) using molecular docking approach. Non covalent interaction between the target ligands was found. Lupeol was found interacting with amino acid (AA) residues in the catalytic domain of MMP-1 with 3 hydrogen bonds (H-bond) formation, phytol with 1 and doxycycline with 2 H-bonds, whereas betulin and lupeol acetate were not able to form any H-bond with the AA residues in the catalytic site of the target protein. However, hydrophobic interaction between these ligands and protein was evident with select residues. The binding affinity of lupeol was highest (binding free energy, Δ G = −8.24 kcal/mol), which was greater than reference drug, doxycycline (Δ G = −8.05 kcal/mol). Lupeol acetate and phytol displayed a Δ G value of −7.12 and −7.06 kcal/mol, respectively, whereas betulin holds less binding affinity for the target receptor (Δ G = −4.66 kcal/mol). In silico pharmacokinetic studies demonstrated drug-like properties of the ligand compounds. This study shows that hydroxyl groups present in the ligands play a substantial role in establishing protein ligand interaction via hydrogen bonding.

In Silico Molecular Docking Simulation of Chromolaena Odorata Phytoconstituents Against Matrix Metalloproteinase Proteins – 9 (MMP-9)

“…Another study by Yasmeen et. al displayed that phytol showed a binding affinity of -7.06 kcal/mol with second highest drug score and could be a potent inhibitory drug for MMP-1 along with potentially safe to be developed into active pharmaceutical drug against MMP-1 [10].…”

GC/MS Profiling, Anti-Collagenase, Anti-Elastase, Anti-Tyrosinase and Anti-Hyaluronidase Activities of a Stenocarpus sinuatus Leaves Extract

“…In It also exhibited antioxidant, anti-inflammatory, antimicrobial, cytotoxic, and immune-modulating activities [ 53 ]. Previous molecular docking studies revealed that phytol can bind to amino acid residues in the catalytic domain of MMP-1 (collagenase enzyme), with binding energy (−7.06 kcal/mol) comparable to that (−8.05 kcal/mol) of the reference compound doxycycline [ 54 ].…”

3,4,3′-Tri-O-methylellagic acid as an anticancer agent:in vitroandin silicostudies

“…7 ), meaning it could still be considered to have good potential as an oral drug as a drug candidate is usually described as having low appropriateness as an oral medication if it does not meet multiple standards. 33 This theoretical information could then be used as initial data for experimental testing considerations.…”