title: Anti-HIV-1 phorbol esters from the seeds of Croton tiglium.
abstract: Five phorbol diesters, together with three known ones, were isolated from a MeOH extract of the seeds of Croton tiglium, and their structures were determined by spectroscopic methods and selective hydrolysis of acyl groups. These 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 and 12-O-decanoylphorbol-13-(2-methylbutyrate) effectively inhibited the cytopathic effect of HIV-1 [complete inhibitory concentration (IC100) values of 7.6 ng/ml and 7.81 microg/ml, and minimum cytotoxic concentration (CC0) value of 62.5 and 31.3 microg/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 most 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).
authors.affiliation: Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
authors.forename: S
authors.initials: S
authors.lastname: El-Mekkawy
authors.forename: M R
authors.initials: MR
authors.lastname: Meselhy
authors.forename: N
authors.initials: N
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Hattori
authors.forename: T
authors.initials: T
authors.lastname: Kawahata
authors.forename: T
authors.initials: T
authors.lastname: Otake
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000302:isolation & purification*; D002460:Cell Line; D002855:Chromatography, Thin Layer; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004789:Enzyme Activation; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D051379:Mice; D010703:Phorbol Esters / Q000737:chemistry / Q000302:isolation & purification*; D010946:Plants, Medicinal / Q000737:chemistry*; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D012639:Seeds / Q000737:chemistry
chemical_list: D019380:Anti-HIV Agents; D010703:Phorbol Esters; D011493:Protein Kinase C