Characterization of Nine Compounds Isolated from the Acid Hydrolysate of Lonicera fulvotomentosa Hsu et S. C. Cheng and Evaluation of Their In Vitro Activity towards HIV Protease.
In this study, we isolated nine compounds from the acid hydrolysate of the flower buds of Lonicera fulvotomentosa Hsu et S. C. Cheng and characterized their chemical structures using 1H-NMR, 13C-NMR, and electron ionization mass spectroscopy (EI-MS). These compounds were identified as β-sitosterol (1), 5,5'-dibutoxy-2,2'-bifuran (2), nonacosane-10-ol (3), ethyl (3β)-3,23-dihydroxyolean-12-en-28-oate (4), oleanolic acid (5), ethyl caffeate (6), caffeic acid (7), isovanillin (8), and hederagenin (9), with 4 as a new triterpene compound. Inhibitory activity against human immunodeficiency virus (HIV) protease was also evaluated for the compounds, and only ethyl caffeate, caffeic acid, and isovanillin (6, 7, and 8) exhibited inhibitory effects, with IC50 values of 1.0 μM, 1.5 μM, and 3.5 μM, respectively. Molecular docking with energy minimization and subsequent molecular dynamic (MD) simulation showed that ethyl caffeate and caffeic acid bound to the active site of HIV protease, while isovanillin drifted out from the active site and dissociated into bulk water during MD simulations, and most of the binding residues of HIV protease have been previously identified for HIV protease inhibitors. These results suggest that caffeic acid derivatives may possess inhibitory activities towards HIV protease other than previously reported inhibitory activities against HIV integrase, and thus ethyl caffeate and caffeic acid could be used as lead compounds in developing potential HIV protease inhibitors, and possibly even dual-function inhibitors against HIV.
['Wang|Xia|X|', 'Wei|Ying|Y|', 'Tian|Wei-Yi|WY|', 'Sakharkar|Meena Kishore|MK|', 'Liu|Qing|Q|', 'Yang|Xin|X|', 'Zhou|Yan-Zi|YZ|', 'Mou|Cheng-Li|CL|', 'Cai|Gui-Lan|GL|', 'Yang|Jian|J|']
D020134:Catalytic Domain D016333:HIV Protease D017320:HIV Protease Inhibitors D015497:HIV-1 D031239:Lonicera D013058:Mass Spectrometry D062105:Molecular Docking Simulation D056004:Molecular Dynamics Simulation D015394:Molecular Structure D064209:Phytochemicals D010936:Plant Extracts
acid hydrolysate Lonicera fulvotomentosa Hsu et S. C. Cheng HIV protease molecular docking inhibitor