Synthesis and cytotoxicity of novel 20-O-linked homocamptothecin ester derivatives as potent topoisomerase I inhibitors.
In an attempt to improve the antitumor activity of homocamptothecins (hCPTs), a series of novel 20-O-linked hCPT ester derivatives were first designed and synthesized based on a synthetic route, by which hCPTs are acylated with different substituted phenoxyacetic acid ester derivatives. Most of the derivatives were assayed for in vitro cytotoxicity against six human cancer cell lines KB, KB/VCR, A549, HCT-8, Bel7402, and A2780, and most of the assayed compounds exhibited good antiproliferative activity on these tumor cell lines especially on KB.
a College of Pharmacy, State Key Laboratory of Medicinal Chemical Biology, State Key Laboratory of Elemento-Organic Chemistry and Tianjin Key Laboratory of Molecular Drug Research, Nankai University , Tianjin , 300071 , China.
Di-Zao
DZ
Li
Cun-Ying
CY
Wang
Rui-Hua
RH
Liu
Yan-Ming
YM
Wang
Teng-Fei
TF
Ji
Yu-Rong
YR
Li
Xian-Dao
XD
Pan
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004952:Esters; D006801:Humans; D020128:Inhibitory Concentration 50; D007624:KB Cells; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004952:Esters; D059004:Topoisomerase I Inhibitors; C120029:homocamptothecin; D002166:Camptothecin