Anti-HIV-1 phorbol esters from the seeds of Croton tiglium

Five phorbol diesters, together with three known ones, were isolated from a MeOH extract of the seeds of Croton tiglium, and their structures were det ermined by spectroscopic methods and selective hydrolysis of acyl groups. T hese compounds were assessed for their abilities to inhibit an HIV-induced cytopathic effect (CPE) on MT-4 cells and to activate protein kinase C (PKC ) associated with tumor-promoting action. 12-O-Acetylphorbol-13-decanoate a nd 12-O-decanoylphorbol-13-(2-methylbutyrate) effectively inhibited the cyt opathic effect of HIV-1 [complete inhibitory concentration (IC100) values o f 7.6 ng/ml and 7.81 mu g/ml, and minimum cytotoxic concentration (CC0) val ue of 62.5 and 31.3 mu g/ml, respectively]; however, 12-O-acetylphorbol-13- decanoate showed no activation of PKC at concentrations of 10 and 100 ng/ml . 12-O-Tetradecanoylphorbol-13-acetate (TPA) was found to be not only the m ost potent inhibitor of HIV-1-induced CPE (IC100 value of 0.48 ng/ml), but also the most potent activator of PKC (100% activation at 10 ng/ml). (C) 20 00 Elsevier Science Ltd. All rights reserved.