Chemical constituents from the stems of Dendrobium gratiosissimum and their biological activities

Eight C-6-C-3-based bibenzyl derivatives (dengraphenols A-G, K), three mono-bibenzyls (dengraphenols I, L-M), one bis-bibenzyl (dengraphenol H), one oxyneolignane (dengraphenol J), one phenanthrene (dengraphenol N), and one picrotoxane-type sesquiterpene (dengrasusane A) were isolated from the stems of Dendrobium gratio-sissimum. The resolution of dengraphenols A-J by chiral HPLC afforded ten pairs of enantiomers [(+/-)-den-graphenols A-J]. Their structures with absolute configurations were elucidated on the basis of comprehensive spectroscopic analyses, computational calculation methods and single-crystal X-ray diffraction, among which twenty-four [(+/-)-dengraphenols A-E, (+)-dengraphenol F, (+/-)-dengraphenols G-J, dengraphenols K-N, den-grasusane A] were undescribed. Ten compounds [(+/-)-dengraphenol B, (+/-)-dengraphenols D-E, (+/-)-den-graphenol H, (-)-dengraphenol I and dengraphenol N)] showed potent cytotoxicity against eight human cancer cell lines (A431, A2780, H460, HCT8, BGC823, SW1990, Daoy, and HGC27) with IC50 values of 3.77-9.75 mu M. At a concentration of 10 mu M, (-)-dengraphenol C, (+/-)-dengraphenol F, and (+/-)-dengraphenol K exhibited remarkable hepatoprotective activity against APAP-induced toxicity with a cell survival rate of 65.8%, 70.6% and 73.5%, respectively; dengraphenol N displayed significant anti-inflammatory effects; and dengraphenol K showed strong inhibitory activity against alpha-glucosidase with IC50 values of 5.71 mu M. These results would provide potential compounds for drug discovery.