Serratene triterpenoids from Lycopodium cernuum L. as α-glucosidase inhibitors: Identification, structure–activity relationship and molecular docking studies

Abstract

Phytochemical investigation of Lycopodium cernuum L. afforded seven undescribed serratene triterpenoids named 3β, 21β-dihydroxyserra-14-en-24-oic acid-3β-(5′-hydroxybenzoate) (1), 3β, 21β, 24-trihydroxyserrat-14-en-3β-(5′-hydroxyl benzoate) (2), 3β, 14α, 15α, 21β-tetrahydroxyserratane-24-methyl ester (3), 3β, 14α, 21β-trihydroxyserratane-15α-(4′-methoxy-5′-hydroxybenzoate)-24-methyl ester (4), 3β, 14α, 21β-trihydroxyserratane-15α-(4′-methoxy-5′-hydroxybenzoate) (5), 3β-hydroxy-21β-acetate-16-oxoserrat-14-en-24-oic acid (6), 3β, 21β-dihydroxy-16α, 29-epoxyserrat-14-en-24-methyl ester (7), together with eleven known compounds (8–18), whose chemical structures were elucidated through spectroscopic analysis of HRESIMS, 1D NMR, 2D NMR and comparison between the literature. All compounds were evaluated for their α-glucosidase inhibitory activity for the first time. The results showed that compounds 1, 2, 4, 5, 6, 10, 13, 15, and 16 were among the most potent α-glucosidase inhibitors, with IC50 values ranging from 23.22 ± 0.64 to 50.65 ± 0.82 μM. Structure–activity relationship (SAR) studies indicated that the combined properties of the 5-hydroxybenzoate moiety at C-3, β-OH at C-21, COOH- at C-24, and Δ14,15 groups enabled an increase in the α-glucosidase inhibitory effect. In addition, molecular docking studies showed that the potential inhibitors mainly interact with key amino acid residues in the active site of α-glucosidase through hydrogen bonds and hydrophobic forces.