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

Phytochemical investigation of Lycopodium cernuum L. afforded seven undescribed serratene triterpenoids named 3 β, 21 β- dihydroxyserra-14-en-24-oic acid-3 β- (5′-hydroxybenzoate) ( 1 ), 3 β, 21 β , 24-trihydroxyserrat-14-en-3 β -(5′-hydroxyl benzoate) ( 2 ), 3 β , 14 α , 15 α , 21 β -tetrahydroxyserratane-24-methyl ester ( 3 ), 3 β , 14 α , 21 β -trihydroxyserratane-15 α -(4′-methoxy-5′-hydroxybenzoate)-24-methyl ester ( 4 ), 3 β , 14 α , 21 β -trihydroxyserratane-15 α -(4′-methoxy-5′-hydroxybenzoate) ( 5 ), 3 β -hydroxy-21 β -acetate-16-oxoserrat-14-en-24-oic acid ( 6 ), 3 β , 21 β -dihydroxy-16 α , 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 IC 50 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 Δ 14,15 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 .