| Stilbenes are naturally occurring compounds found in a wide range of plant sources. One well-characterized stilbene, resveratrol, has demonstrated potent anti-cancer, anti-inflammatory and anti-oxidant activities. Piceatannol, pinosylvin, and rhapontigenin are stilbenes that are structurally similar to resveratrol and possess varying degrees of pharmacological activities.; Simple, selective, accurate, reproducible and isocratic high-performance liquid chromatographic (HPLC) methods were developed and validated for the first time for the quantification of piceatannol, pinosylvin, and rhapontigenin. A novel method for the preparative enzymatic synthesis of rhapontigenin from its parent compound was developed and the resulting rhapontigenin was verified using nuclear magnetic resonance (NMR) and Mass Spectrometry (MS).; The metabolic transformation of piceatannol, pinosylvin, and rhapontigenin in male rat liver microsomes was determined. Metabolic products were identified using HPLC and verified using mass spectrometry. All three stilbenes underwent extensive glucuronidation. E and Z-resveratrol were the minor oxidative metabolites of pinosylvin in phase I metabolism.; The pharmacokinetic parameters following intravenous administration of piceatannol, pinosylvin, and rhapontigenin in Sprague-Dawley male rats were characterized and modelled using WinNonlinRTM pharmacokinetic software. Each stilbene underwent extensive glucuronidation and was predominately eliminated via non-urinary routes. All three stilbenes were highly distributed into the tissue and were highly extracted. The detectable serum half-lives of these compounds appears to be relatively short. However, utilizing urinary concentration-time data, much longer elimination half-lives was revealed.; Piceatannol, pinosylvin, and rhapontigenin were tested in several cancer cell lines and were found to be active anti-cancer agents. The activities of these compounds vary from one another and are dependent on differences in methoxy and hydroxyl moiety substitutions. It also appears that the potency of these stilbenes is cancer cell type dependent.; The pharmacodynamic activities of piceatannol and rhapontigenin in an experimental model of ulcerative colitis, and piceatannol and pinosylvin in an experimental model of colonic adenocarcinoma were determined. The oral administration of these selected stilbenes reduced the colonic damage in these experimental models. In addition, in parallel to the in vitro cell line activity, pinosylvin and piceatannol had significant activity in an in vivo azoxymethane-induced model of colon adenocarcinoma. Stilbenes are bioactive natural products that require experimental pharmaceutical studies. |
