Synthesis and anticancer activity evaluation of 7-oxygen-substituted and 8,17-epoxydized 1,2-didehydro-3-ox-14-deoxyandrographolide derivatives

Two novel series of 1,2-didehydro-7-hydroxy-3-ox-14-deoxyandrographolide and 1,2-didehydro-8,17-epoxy-3-ox-14-deoxyandrographolide derivatives were designed, synthesized and evaluated for their cytotoxic activity in vitro against two human cancer cell lines HCT-116 (human colon cancer) and MCF-7 (human breast cancer). Most tested compounds, especially those of the first series, displayed better inhibitory activity on both HCT-116 and MCF-7 cells than andrographolide. HCT-116 cells were found to be more sensitive to tested compounds than MCF-7, and compound 13b exhibited the most potent activity against HCT-116, with an IC50 value of 7.32 mu M. Further anti-cancer mechanistic investigation demonstrated that compound 13b effectively suppressed the growth of HCT-116 cells by triggering early and late cellular apoptosis in a concentration-dependent manner and arresting cell cycle in S phase.

Automated summary

Two novel series of derivatives were synthesized and evaluated for their cytotoxic activity against colon cancer and breast cancer cells. Most compounds exhibited better inhibitory activity than the reference compound, and HCT-116 cells were more sensitive to the compounds.