Polycyclic polyprenylated acylphloroglucinols from the fruit of Hypericum addingtonii N. Robson and their α-glucosidase inhibitory activity

Abstract

This paper presents the first chemical investigation of the fruit of Hypericum addingtonii N. Robson, leading to the isolation of seven previously undescribed compounds and 14 known polycyclic polyprenylated acylphloroglucinols. The seven unreported compounds included four terpenoidal polycyclic polyprenylated acylphloroglucinols, hypertonii A–D (1–4), and three anthrone derivatives, hyperxanthone G–H (19–21). The structures of the undescribed compounds were confirmed using spectroscopic analyses, electronic circular dichroism, and nuclear magnetic resonance calculations. The α-glucosidase inhibitory activities of all the isolated compounds were evaluated. Fifteen compounds showed remarkable activity with half maximal inhibitory concentrations (IC₅₀) ranging from 1.13 ± 0.26 to 42.7 ± 9.00 µM. The most active compound (7) showed strong activity (IC₅₀ = 1.13 ± 0.26 µM), and compounds 11, 1, 12, and 18 displayed considerable activity (IC₅₀ = 2.85 ± 0.15, 3.03 ± 0.15, 3.16 ± 0.21, and 3.55 ± 0.45 µM, respectively). Kinetic studies showed that the five most active compounds were mixed-type α-glucosidase inhibitors. Molecular docking analysis revealed that these active compounds had good binding affinity to α-glucosidase.