Synthesis and antitumor activity of emodin quaternary ammonium salt derivatives

A series of new emodin derivatives modified at the C-3 and the C-6 positions were synthesized, and evaluated for their anticancer activities in vitro and in vivo. Among them, Compounds 5g and 5h had more significant antiproliferative ability against HepG2, BGC-823, AGS cancer cell lines and low cytotoxicity to HELF normal cell line, respectively. Compounds 5g and 5h induced AGS cell cycle arrest at G0/G1 phase and induce apoptosis via activation of caspase-3 and caspase-9 enzyme. In vivo studies using H22 xenografts in Kunming mice were conducted with 5g and 5h. The results revealed that the medium dosage group (10 mg/kg) of 5g and the high dosage group (25 mg/kg) of 5h showed significant antitumor activity compared to the control group.

Graphical abstractTwenty new emodin derivatives were synthesized and investigated their anticancer activities. Compounds 5g and 5h showed significant antiproliferative and apoptosis abilities in vitro and exerted preferable proliferation inhibition effect in vivo.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Twenty novel emodin derivatives were synthesized. ► Compounds 5g and 5h showed significant anticancer activity in vitro and in vivo. ► Compounds 5g and 5h induced apoptosis through caspase-9 and caspase-3 activation. ► Compounds 5g and 5h arrested cell cycle progression at the G0/G1 phase in AGS cells.