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.
Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Fuzhou University, Fujian 350108, PR China.
Jingwei
J
Shao
Fengsen
F
Zhang
Zedong
Z
Bai
Conghui
C
Wang
Yaofeng
Y
Yuan
Wenfeng
W
Wang
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004642:Emodin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012492:Salts / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D000644:Quaternary Ammonium Compounds; D012492:Salts; D004642:Emodin