Isolation, Structure Elucidation, Synthesis, and Cytotoxic Activity of Polyacetylenes and Polyenes from Echinacea pallida

Abstract

This study focuses on presenting an overview of recent results on the cytotoxic activity of polyacetylenes and polyenes isolated from Echinacea pallida. In a search for biologically active compounds from plants of the genus Echinacea, the lipophilic extract from E. pallida roots was characterized by a higher cytotoxic activity if compared with the other tested species. A subsequent bioassay-guided fractionation allowed the isolation and structure elucidation of ten polyacetylenes and polyenes from E. pallida roots. The isolated secondary metabolites were tested for their cytotoxic activity on selected human cancer cell lines and (8Z,13Z)-pentadeca-8,13-dien-11-yn-2-one was the most active constituent, particularly on the colonic COLO320 cancer cells (IC50 = 2.3 ± 0.3 μM) and breast carcinoma MCF-7 cancer cells (IC50 = 2.5 ± 0.7 μM). Arrest of cell cycle in the G1 phase and induction of apoptosis were found to be involved in its mechanism of action. Due to the difficult purification of this compound from the plant material, its first total synthesis was also described. A HPLC stability study of this natural product finally indicated that its cytotoxic activity can be mainly attributed to the genuine, not oxidized, molecule. These results indicated that polyacetylenes and polyenes from E. pallida are effective in inhibiting cancer cell proliferation and incorporation of enriched fractions of these compounds in the diet may be useful for cancer prevention. The most active compound represents also an interesting lead structure for the development of new antiproliferative agents.