Diabetes mellitus remains a significant global health challenge, necessitating the discovery of novel therapeutic interventions. This study elucidated the inhibitory potential of phytochemicals derived from the African star apple (Chrysophyllum albidum (C. albidum)) against two critical enzymes implicated in diabetes pathogenesis: dipeptidyl peptidase IV (DPP-IV) and adenosine deaminase (ADA). A multi-pronged approach integrating in vitro enzyme inhibition assays and in silico molecular docking simulations was employed. Aqueous extracts from various C. albidum fruit parts were evaluated for enzyme inhibition using colorimetric assays. Molecular docking studies were performed using the crystal structures of DPP-IV (PDB ID: 2ONC) and ADA (PDB ID: 3IAR) to investigate binding interactions and identify potential hit compounds using autodock-vina. In vitro assays revealed potent, dose-dependent inhibition of both DPP-IV and ADA by the aqueous extracts, with the fruit's seed coat extract exhibiting the most promising activity (IC50 = 4.88 μg/mL and 18.25 μg/mL against DPP-IV and ADA, respectively). Molecular docking unveiled several C. albidum hits, including CIDs 562,128 (-9.569), 6,430,793 (-9.501), and 23,647,311 (-8.286), and 73,530 (-6.936) exhibiting favorable drug-like properties and binding geometries. This integrative study unveiled the inhibitory potential of C. albidum phytochemicals against DPP-IV and ADA, with a notable correlation between in vitro and in silico data, underscoring the therapeutic promise of this indigenous African plant source for developing novel antidiabetic agents, most importantly the seedcoat.
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