In silico evaluation of the inhibitory property of Holothuria scabra (sea cucumber) with the catalytic domain of matrix metalloproteinase-1 for collagen degradation via interaction of triterpenoid saponins

Abstract

Matrix metalloproteinase-1 (MMP-1) is a collagenase that cleaves the collagen present in the extracellular matrix (ECM), which results in skin wrinkling. In this in silico study, the triterpenoid saponins present from Holothuria scabra (desholothurin A, holothurinoside C, pervicoside C), were studied to determine its inhibitory properties against MMP-1. The approach was done via determining its dermatologic activity, its binding affinity against MMP-1 via molecular docking, followed by its pharmacokinetic properties. Dermatologic activity assessment of each triterpenoid saponins gave a Pa value of 0.408 for desholothurin A, 0.481 for holothurinoside C, and 0.297 for pervicoside C. In molecular docking, all triterpenoid saponins exhibited strong (such as conventional hydrogen bonding) and weak molecular interactions (such as van der Waals forces and carbon-carbon interactions). These molecular interactions was described by binding affinity giving desholothurin A a binding energy of -6.03 kcal/mol (37.79 uM), following holothurinoside C with -5.46 kcal/mol (99.14 uM), and pervicoside C with -3.05 kcal/mol (5480 uM). Lastly, in silico pharmacokinetic studies were done, which demonstrated poor drug-like properties of the compounds.