A new stilbene from Agonis flexuosa leaves and verification of its histamine release inhibitory activity using in silico and in vitro studies

Abstract

This study aimed to explore the phytoconstituents of Agonis flexuosa, F. Myrtaceae and its biological activity. A thorough phytochemical investigation of its leaves led to the isolation of one new stilbene glycoside; (Z)-2,3-dihydroxystilbene-5-O-β-D-glucoside (1), and fifteen known compounds identified as two stilbenes: (Z)-pinosylvin mono methyl ether (2) and (Z)-pinosylvin-3-O-β-D-glucoside (3); six flavanones: (2S)-pinostrobin (4), (2S)-strobopinin (5), (2S)-cryptostobin (6), (2S)-pinocembrin (7), (2S)-dimethylpinocembrin (8) and (2S)-dimethylstrobopinin (9); four flavonoids: quercetin (10), kaempferol-7-O-β-D-glucoside (11), quercetin-3-O-α-D-rhamnoside (12) and quercetin-3-O-β-D-glucoside (13), α-terpineol (14), β-sitosterol (15) and gallic acid (16). The structures of the isolated metabolites were elucidated based upon the interpretation of their 1D and 2D NMR (One Dimensional and Two-Dimensional Nuclear Magnetic Resonance), HR-ESI-MS (High Resolution Electrospray Ionization Mass Spectrometry) and optical rotation. All the isolated compounds were evaluated for their antimicrobial activities. Only compound (6) showed a selective activity against P. aeruginosa with IC50 value of 4.88 µM. In silico virtual screening was done for the isolated compounds on Human histamine H1 receptor (3RZE) downloaded from protein data bank. All the compounds showed certain degree of binding to the protein displaying free binding energies ranging between -11 to -31 kcal/mol. (Z)-2,3-Dihydroxystilbene-5-O-β-D-glucoside (1) showed notable fitting to the active site as evidenced by its free binding energy (∆G) which is computed as -25.09 kcal/mol comparable to diclofenac that displayed (∆G) of -15.00 kcal/mol. In vitro assessment of histamine release inhibitory activity was performed using U937 human monocytes. Compound (1) showed a substantial inhibition to histamine release displaying IC50 value of 0.16 μM.