Discovery and synthesis of rocaglaol derivatives inducing apoptosis in HCT116 cells via suppression of MAPK signaling pathway

Abstract Six rocaglaol derivatives were isolated from Dysoxylum gotadhora, and those compounds showed good cytotoxic activity with IC50 values ranging from 10 to 350 ng/mL against five different cancer cells. Obviously, further total synthesis of rocaglaol derivatives for medical chemistry study is of great significance. Then, twenty six rocaglaol derivatives including 25 new compounds were designed, synthesized, and evaluated for their cytotoxic activities against three human cancer cell lines: human colon cancer cells (HCT116), colorectal cancer stem cells (P6C), and human red leukocyte leukemia cells (HEL), using MTT assay. Most of derivatives showed good cytotoxic activities, with the lowest IC50 being 3.2 nM for HEL cells, which was 169 times stronger than that of the positive control (doxorubicin). Further mechanism study indicated that 11k could significantly suppress MAPK pathway in HCT116 cells, which may responsible for induction of apoptosis and cell cycle arrest.