Synthesis of xanthone derivatives and studies on the inhibition against cancer cells growth and synergistic combinations of them

34 Xanthones were synthesized by microwave assisted technique. Their in vitro inhibition activities against five cell lines growth were evaluated. The SAR has been thoroughly discussed. 7-Bromo-1,3-dihydroxy-9H-xanthen-9-one (3-1) was confirmed as the most active agent against MDA-MB-231 cell line growth with an IC50 of 0.46 ± 0.03 μM. Combination of 3-1 and 5,6-dimethylxanthone-4-acetic acid (DMXAA) showed the best synergistic effect. Apoptosis analysis indicated different contributions of early/late apoptosis and necrosis to cell death for both monomers and the combination. Western Blot implied that the combination regulated p53/MDM2 to a better healthy state. Furthermore, 3-1 and DMXAA arrested more cells on G2/M phase; while the combination arrested more cells on S phase. All the evidences support that the 3-1/DMXAA combination is a better anti-cancer therapy. [Display omitted] •DMXAA synergized 7-bromo-1,3-dihydroxyl 9H-xanthen-9-one (LJ-1) by 10 times the activity.•DMXAA/LJ-1 showed different distribution in early, late apoptosis and necrosis compared to both monomers.•DMXAA/LJ-1 combination regulated p53-MDM2 most positively.•DMXAA/LJ-1 combination arrested more cells on S phase.