Antiproliferative properties of xanthones from Calophyllum inophyllum and Calophyllum soulattri towards human cancer cell lines

Abstract

Extensive chromatographic isolation and purification on the extracts of the stem bark of Calophyllum inophyllum and Calophyllum soulattri resulted in eleven xanthones. These xanthones were identified as inophinnin (1), inophinone (2), soulattrin (3) and phylattrin (4), pyranojacareubin (5), rheediaxanthone A (6), macluraxanthone (7), 4-hydroxyxanthone (8), caloxanthone C (9), brasixanthone B (10) and trapezifolixanthone (11). The structures of these compounds were determined on the basis of spectroscopic analyses such as 1D and 2D-NMR, GCMS, IR and UV. Cytotoxicity assay (MTT) [1] carried out in vitro on all the xanthones using five human cancer cell lines which are SNU-1 (stomach), HeLa (cervical), NCI-H23 (lung), Hep G2 (liver) and K562 (leukemia) indicated good activities for some of these xanthones. Compounds 3 and 7 possessed the strongest anti-proliferative properties with IC50 values ranging from 1.98 to 12.87µM towards all the cell lines. The structure-activity relationship (SAR) among these xanthone derivatives were predicted to be closely related to the existence and nature of the substituent groups on their skeleton. Both bioactive compounds 3 and 7 consist of a pyrano ring fused at C-2 and C-3 of the xanthone skeleton together with a prenyl (3-methyl-1-butenyl-) moiety attached at C-5 and C-4, respectively. Conversely, compound 8 which exists as a simple xanthone without any substituent group is inactive to the cell lines. As a conclusion, xanthones exist as potential anti-cancer lead compounds at which the main substituent groups that are corresponded to their cytotoxic properties are pyrano ring and prenyl (3-methyl-1-butenyl-) moiety.