Chiral derivatives of xanthones: applications in Medicinal Chemistry and a new approach in Liquid Chromatography

Fernandes, Carla; Tiritan, Maria Elizabeth; Pinto, Madalena M. M.

Palavras-chave: Xanthones, chiral, enantioselectivity, chiral stationary phases, liquid chromatography.

Resumo: Over several years, the xanthonic derivatives have been the focus of many studies essentially, due their broad range of biological and pharmacological activities. Recently, chiral derivatives of xanthones (CDX) have come to arouse great interest considering both the enantioselectivity studies associated with biological activity as well as chiral chromatography. In a perspective of Medicinal Chemistry, thirty enantiomers corresponding to fifteen pairs of CDX (small molecules), were synthesized and tested to assess the biological/ pharmacological activity, including inhibition of growth of human tumor cell lines, showing in some cases very interesting effects. The most active compound showed values of GI 50 of 32.15 ± 2.03 μ M for A375-C5, 22.55 ± 1.99 μ M for MCF-7, and 14.05 ± 1.82 μ M for NCI-H460. Furthermore, the growth inhibitory effects, in some cases, demonstrated to be depending on the stereochemistry of the CDXs. Besides the potential as new drugs, CDX present structures with interest as chiral selectors for chromatography. In this context some CDX were selected and bound to a chromatographic support to new application as chiral stationary phase in liquid chromatography. New xanthonic chiral stationary phases represent completely different selectors based on small molecules, with promising results, high stability and reproducibility. Thus, it is concluded that CDX have important applications in the field of Medicinal Chemistry not only as potential drugs but also with an application “out of the box” as chiral selectors of new stationary phases for liquid chromatography..

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