Synthesis And Bioactivities Of Marine-Derived Halophenols

Halophenols, the secondary metabolites of various marine algae, ascidians, and sponges, had wide spectrum of bioactivities including antioxidative, antimicrobial, antitumor, antithrombotic, anti-inflammatory, a-glucosidase inhibitory, protein tyrosine phosphatase (PTP1B) inhibitory, and feeding deterrent activities.However, further researches on the bioactivities of the halophenols were greatly limited for their low content in marine algae and the great difficulty of extraction. Therefore, we designed and synthesized two series of halophenols, the halogenated hydroxy diphenylmethanones and the halogenated hydroxy diphenylmethanes. The halophenols were evaluated for their in vitro activities, and primary structure-activity relationships were investigated.Halophenols were prepared from benzoyl chlorides or benzoic acids by chlorination, Friedel-Crafts acylation, halogenation, and demethylation. The structures were confirmed by ESI-MS, HRMS,1H NMR, and 13C NMR spectra. Then the target compounds were evaluated for their in vitro bioactivities, including antioxidative activity, cytoprotective activity against H2O2-induced injury in human umbilical vein endothelial cell (HUVEC), inhibitory activity against protein tyrosine kinase (PTK), and inhibitory effect on vascular smooth muscle cell (VSMC) proliferation. The results showed that the halophenols displayed potent in vitro antioxidative activity and cytoprotective activity. Two bromophenols,2,3'-dibromo-4,5,6'-trihydroxydiphenylmethan-one (13c) and 2,3-dibromo-4,5-dihydroxydiphenylmethanone (15c), exhibited high protective activity against H2O2-induced injury in HUVEC with EC50 values of 0.4μM and 0.8μM, respectively. Some compounds also exhibited good inhibitory activity against PTK and against proliferation of VSMC. The preliminary structure-activity relationships of these compounds were also investigated in order to determine the essential structures required for their bioactivities.