Isomeric Kielcorins and Dihydroxyxanthones: Synthesis, Structure Elucidation, and Inhibitory Activities of Growth of Human Cancer Cell Lines and on the Proliferation of Human Lymphocytes In Vitro

Abstract

The synthesis, structure elucidation, and biological activities of five isomeric xanthonolignoids, (±)-trans-kielcorin C, (±)-cis-kielcorin C, (±)-trans-kielcorin D, (±)-trans-isokielcorin D, and (±)-trans-kielcorin E, are reported. The synthetic approach is based on the oxidative coupling of coniferyl alcohol with an appropriate xanthone. The influence of different oxidizing agents was studied, and the best results were obtained with potassium hexacyanoferrate(III). The structure elucidation was achieved by 2D-NMR techniques such as COSY, HETCOR, HSQC, and HMBC. Long-range C,H connectivities were used to establish the orientation of the substituents on the 1,4-dioxine rings, while NOE experiments were used to determine the configurations of these rings. These xanthonolignoids, as well as (±)-trans-kielcorin, (±)-trans-kielcorin B, (±)-trans-isokielcorin B, and the xanthonic building blocks 3,4-, 1,2-, and 2,3-dihydroxy-9H-xanthen-9-ones, and 2,3-dihydroxy-4-methoxy-9H-xanthen-9-one, were evaluated for their in vitro effect on the growth of three human cancer cell lines, MCF-7 (breast), TK-10 (renal), and UACC-62 (melanoma), and on the proliferation of human lymphocytes.