Semi-synthesis and in vitro anti-tumor effects evaluation of novel xanthohumol derivatives

Abstract Xanthohumol (Xn) is a chalcone compound isolated from Humulus lupulus Linn. and has various biological activities. In this study, eight Xn derivatives were synthesized by Williamson, Mannich, Reimer-Tiemann, and Schiff base reactions, and five cancer cell lines (MDA-MB-231, MCF-7, CNE-2Z, SMMC-7721, H1975) were evaluated for in vitro cytotoxic activity. Among these, 2-(( E )-2,4-dihydroxy-5-(( E )-3-(4-hydroxyphenyl)acryloyl)-6-methoxy-3-(3-methylbut-2-en-1-yl)benzylidene)hydrazine-1-carboximidamide ( 8 ) exhibited the best potent cytotoxic activity against the five cancer cells, with IC 50 values ranging from 4.87 to 14.35 µM. Wound-healing and transwell assays also showed that compound 8 could better inhibit the migration and invasion of MDA-MB-231 cells, and western blotting assays showed that it could reduce protein expression of HIF-1α, MMP-2 and MMP-9. In addition, flow cytometry assays showed that compound 8 could induce apoptosis in MDA-MB-231 cells by up-regulation of Bax and down-regulation of Bcl-2 and Akt expression.