Withanolides from Jaborosa cabrerae

MANUELA E. GARCÍA; ALEXIS WÖLFEL SANCHEZ; GLORIA E. BARBOZA; JUAN C. OBERTI; CARLA RÍOS-LUCI; JOSÉ M. PADRÓN; VIVIANA E. NICOTRA; ANA ESTÉVEZ-BRAUN ; ANGEL G. RAVELO

Campinas

Congreso; ESPCA on Natural Products, Medicinal Chemistry and Organic Synthesis; 2011

Universidad de San Pablo

Natural products play a highly significant role in the drug discovery and development process. This was particularly evident in the areas of cancer and infectious diseases, where over 60% and 75% of these drugs, respectively, were shown to be of natural origin. Jaborosa Juss. is one of the five largest genera of South American Solanaceae. Withanolides are a group of oxygenated steroidal lactones isolated from several genera of the plant family Solanaceae; many of them exhibit a variety of biological activities. The aerial parts of J.cabrerae were air dried and extracted with ethanol. After concentration and defatting, the residue was fractionated by a combination of chromatographic techniques, ultimately yielded five sativolide withanolides: compound 1, jaborosalactones R, S, 38, and 39; together with two trechonolide withanolides epimeric at C-23, trechonolide A and jaborosalactone 32. Some genera of the Solanaceae family contain withanolides with exclusive interesting arrangements which can be considered at a generic level as chemotaxonomic markers. Sativolide and trechonolide withanolides belong particularly to Jaborosa sect. Lonchestigma (Dunal) Wettstein in which J. cabrerae form part of. The results obtained in our study agree with this statement. Some withanolides have exhibited antiproliferative activity against human breast cancer cell lines.4 Thus, jaborosalactone 38, was able to induce growth inhibition in all cell lines tested (GI50= 2.6-4.1 uM). Considering their activity and the amount isolated (438 mg), we decided to prepare a small set of derivatives . All new compounds were fully characterized by 1D and 2D NMR spectroscopic studies. The in vitro antiproliferative activity of all natural compounds and semisynthetic derivatives, was evaluated. The analysis of the antiproliferative activity support those of other studies on the structure-activity relationship of withanolides.