Studi In Silico Senyawa Aktif dalam Buah Kersen (Muntingia calabura L.) sebagai Antidiabetes pada Reseptor PPAR-γ (2GTK)

Diabetes mellitus is a chronic metabolic disease characterized by impaired glucose metabolism due to insulin resistance. Activation of the PPAR-γ receptor is known to increase insulin sensitivity, making it a target for type 2 diabetes therapy. This study aims to evaluate the potential of active compounds from the kersen fruit (Muntingia calabura L.) as PPAR-γ agonists through an in-silico approach. Analysis was conducted using Lipinski's Rule of Five prediction, ADME and toxicity assessment, pharmacophore modeling, and molecular docking simulation against the PPAR-γ protein (code 2GTK). Results showed that all compounds met oral bioavailability criteria, and most compounds exhibited good ADME profiles and low toxicity. The best pharmacophore model had an AUC value of 0.71 and an EF of 1.1. The compound 7,3',4'-trimethoxyisoflavone showed the best affinity with a Gibbs free energy value of –9.40 kcal/mol and an inhibition constant of 0.12925 μM, and interacted with important amino acid residues of PPAR-γ (SER289, HIS323, HIS449, TYR473). However, toxicity aspects, namely mutagenicity and carcinogenicity, are obstacles that must be overcome by conducting further tests.