Salazinic Acid and Norlobaridone from the Lichen Hypotrachyna cirrhata : Antioxidant Activity, α-Glucosidase Inhibitory and Molecular Docking Studies.

The present study was intended for the identification of secondary metabolites in acetone extract of the lichen Hypotrachyna cirrhata using UPLC-ESI-QToF-MS/MS and the detection of bioactive compounds. This study led to the identification of 22 metabolites based on their MS/MS spectra, accurate molecular masses, molecular formula from a comparison of the literature database (DNP), and fragmentation patterns. In addition, potent antioxidant and α-glucosidase inhibitory potentials of acetone extract of H. cirrhata motivated us to isolate 10 metabolites, which were characterized as salazinic acid ( 11 ), norlobaridone ( 12 ), atranorin ( 13 ), lecanoric acid ( 14 ), lichesterinic acid ( 15 ), protolichesterinic acid ( 16 ), methyl hematommate ( 17 ), iso-rhizonic acid ( 18 ), atranol ( 19 ), and methylatratate ( 20) based on their spectral data. All these isolates were assessed for their free radicals scavenging, radical-induced DNA damage, and intestinal α-glucosidase inhibitory activities. The results indicated that norlobaridone ( 12 ), lecanoric acid ( 14 ), methyl hematommate (17 ), and atranol ( 19 ) showed potent antioxidant activity, while depsidones (salazinic acid ( 11 ), norlobaridone ( 12 )) and a monophenolic compound (iso-rhizonic acid, ( 18 )) displayed significant intestinal α-glucosidase inhibitory activities ( p < 0.001), which is comparable to standard acarbose. These results were further correlated with molecular docking studies, which indicated that the alkyl chain of norlobaridione ( 12 ) is hooked into the finger-like cavity of the allosteric pocket; moreover, it also established Van der Waals interactions with hydrophobic residues of the allosteric pocket. Thus, the potency of norlobaridone to inhibit α-glucosidase enzyme might be associated with its allosteric binding. Also, MM-GBSA (Molecular Mechanics-Generalized Born Surface Area) binding free energies of salazinic acid ( 11 ) and norlobaridone ( 12 ) were superior to acarbose and may have contributed to their high activity compared to acarbose.