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Synthesis and Cytotoxicity of Novel 20-O-linked (±)-Homocamptothecin Ester Derivatives
LI Dizao 1 * #,Pan Xiandao 2
1.College of Pharmacy, State key Laboratory of Medicinal Chemical Biology and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071
2. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People’s Republic of China
*Correspondence author
#Submitted by
Subject:
Funding: the Research Fund for the Doctoral Program of Higher Education of China（No.Grant No. 20110031120048）, the Fundamental Research Funds for the Central Universities of China （No.No. 65011141）
Opened online:13 June 2013
Accepted by: none
Citation: LI Dizao,Pan Xiandao.Synthesis and Cytotoxicity of Novel 20-O-linked (±)-Homocamptothecin Ester Derivatives[OL]. [13 June 2013] http://en.paper.edu.cn/en_releasepaper/content/4545343
 
 
(±)-Homocamptothecin (hCPT) is a semisynthetic analogue of camptothecin (CPT) with a seven-membered β-hydroxylactone resulting from the insertion of a methylene (-CH2-) spacer between the alcohol moiety and the carboxyl group of the classical six-membered α-hydroxylactone ring of CPT. This E-ring modification provides a less reactive lactone with enhanced stability and decreased protein binding in human plasma and rather appears to improve instead of impairing its activity against topoisomerase I (Topo I) compared to CPT. In an attempt to improve the antitumor activity of homocamptothecins, a series of novel 20-O-linked hCPT ester derivatives were first designed and synthesized based on a synthetic route which acylates semi-synthesized (±)-homocamptothecin with different substituted phenoxyacetic acid ester derivatives. Most of the synthesized hCPT ester 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. Here the synthesis and the in vitro antitumor evaluation of 20-O-linked substituted phenoxyacetic acid ester derivatives of (±)-hCPTs are reported.
Keywords:(±)-Homocamptothecin ester; Synthesis; Cytotoxicity
 
 
 

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