Synthesis, antitumor activity evaluation and mechanistic study of novel hederacolchiside A1 derivatives bearing an aryl triazole moiety.
In an attempt to arrive at a more potent antitumor agent than the parent natural saponin hederacolchiside A1, 23 hederacolchiside A1 derivatives (4a-4w) were synthesized via Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition and screened in vitro for cytotoxicity against six human cancer cell lines. The structure-activity relationship of these compounds was elucidated, and the biological screening results showed that most of the compounds exhibited moderate to high levels of antitumor activities against the tested cell lines and some of them displayed more potent inhibitory activities compared with hederacolchiside A1. Compound 4f showed a 2- to 7-fold more potent activity than hederacolchiside A1. The mechanistic study of 4f revealed that this compound can induce cell apoptosis in HepG2 cells via mitochondrial-mediated intrinsic pathways.
['Li|Hui-Ning|HN|', 'Wang|Hui|H|', 'Wang|Zhi-Peng|ZP|', 'Yan|Hai-Ning|HN|', 'Zhang|Miao|M|', 'Liu|Yang|Y|', 'Cheng|Mao-Sheng|MS|']
D000970:Antineoplastic Agents D017209:Apoptosis D002453:Cell Cycle D045744:Cell Line, Tumor D049109:Cell Proliferation D002470:Cell Survival D004305:Dose-Response Relationship, Drug D004354:Drug Screening Assays, Antitumor D006801:Humans D053078:Membrane Potential, Mitochondrial D015394:Molecular Structure D012503:Saponins D013329:Structure-Activity Relationship D014230:Triazoles
Antitumor activity Saponin Structure-activity relationship Apoptosis Hederacolchiside A(1)