Structural Characterization, In Vitro Antidiabetic Activity, and Molecular Docking Studies of Isolated Compounds From <i>Allamanda cathartica</i>

Allamanda cathartica is a perennial shrub, traditionally used for the treatment of several ailments, including jaundice, malaria, and enlargement of the spleen. Besides ornamental values, the plant also possesses a wide variety of medicinal properties due to the presence of bioactive secondary metabolites of different chemical classes. The present work describes the phytochemical investigation of the leaf part of A. cathartica, which resulted in the isolation of five secondary metabolites (ACL 1-5) of different classes, including β-sitosterol (ACL-1), β-sitosterol glucoside (ACL-2), ursolic acid (ACL-3), plumieride (ACL-4), and pinitol (ACL-5). The compound ACL-5 was reported for the first time from the species. All the compounds were characterized by ¹H NMR, ¹³C NMR, 2D NMR, and HRMS spectral analysis. Further to the plant extract, all the fractions and five isolated compounds were screened for in vitro α-amylase and α-glucosidase activity. The isolated compounds exhibited notable inhibitory activity against carbohydrate-hydrolyzing enzymes. For α-amylase inhibition, IC₅₀ values ranged from 522.95 to 662.67 µg/mL, with plumieride showing the highest potency at a concentration of 522.95 µg/mL and pinitol acetate the lowest at 662.67 µg/mL. Similarly, for α-glucosidase inhibition, IC₅₀ values ranged from 576.82 to 691.12 µg/mL, where plumieride again demonstrated the strongest activity at 576.82 µg/mL and pinitol acetate the lowest at 662.67 µg/mL. In support, all isolated compounds were taken further for molecular modelling studies to observe the rationale of our in vitro studies. Therefore, this work concludes that the isolated compounds ACL-4 and ACL-5 have demonstrated strong antidiabetic potential, with ACL-4 having a somewhat more powerful antidiabetic effect than ACL-5, according to both in vitro and docking experiments.