ANTIDIABETIC ACTIVITY OF NOVEL CHROMENE COMPOUND ISOLATED FROM PEPEROMIA PELLUCIDA L. KUNTH AND IN SILICO STUDY AGAINST DPP-IV, ALPHA-GLUCOSIDASE, ALPHA-AMYLASE, AND ALDOSE REDUCTASE FOR BLOOD GLUCOSE HOMEOSTASIS

Abstract

Objective: During the outbreak of COVID-19, diabetes mellitus (DM) and cardiovascular disease (CVD) become risk factors for severe adverse clinical outcomes in COVID-19 patients. DM is a complex metabolic disease originating from a process of requiring adequate insulin or due to insulin resistance. This in silico study reveals the molecular interaction of Peperochromene A ((S)-2-methyl-2-(4-methylpent-3-enyl)-6-(propan-2-ylidene)-3,4,6,7-tetrahydropyrano[4,3-g]chromen-9(2H)-one), a novel chromene compound isolated from Peperomia pellucida with four proteins involved in the homeostasis of blood glucose, namely dipeptidylpeptidase-IV (DPP-IV), α-glucosidase, α-amylase, and aldose reductase.
 Methods: Molecular docking simulation of the ligands was performed by employing AutoDock 4.2 embedded in LigandScout at a certain position determined automatically by the program. The default parameters of the automatic settings were used to set the genetic algorithm parameters.
 Results: Peperochromene A could interact with all four targets; however, it binds to alpha-glucosidase and α-amylase with Ki (inhibition constant) value better than that of acarbose, the enzymes’ known inhibitor. This chromene compound also reveals an inhibition constant to aldose reductase similar with that of the enzyme inhibitor.
 Conclusion: The chromene isolated from Peperomia pellucida is the potential to be developed as an inhibitor of the proteins involved in the homeostasis of blood glucose; thus, it can be further explored for its antidiabetic activity.