Design, synthesis and antimalarial/anticancer evaluation of spermidine linked artemisinin conjugates designed to exploit polyamine transporters in Plasmodium falciparum and HL-60 cancer cell lines

被引：49
作者：
Chadwick, James [1 ]
Jones, Michael [1 ]
Mercer, Amy E. [2 ]
Stocks, Paul A. [3 ]
Ward, Stephen A. [3 ]
Park, B. Kevin [2 ]
O'Neill, Paul M. [1 ,2 ]
机构：
[1] Univ Liverpool, Dept Chem, Liverpool L69 7ZD, Merseyside, England
[2] Univ Liverpool, Sch Biomed Sci, Dept Pharmacol & Therapeut, MRC Ctr Drug Safety Sci, Liverpool L69 3GE, Merseyside, England
[3] Univ Liverpool Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 07期
基金：
英国医学研究理事会;
关键词：
Artemisinin; Polyamine; Malaria; Cancer; TUMOR-CELLS; DEPENDENT CYTOTOXICITY; ANTITUMOR EVALUATION; TRIOXANE DIMERS; LEUKEMIA-CELLS; CARBA ANALOGS; FERROUS ION; IN-VITRO; DERIVATIVES; DIHYDROARTEMISININ;
D O I：
10.1016/j.bmc.2010.02.035
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
A series of artemisinin-spermidine conjugates designed to utilise the upregulated polyamine transporter found in cancer cells have been prepared. These conjugates were evaluated against human promyelocytic leukaemia HL-60 cells and chloroquine-sensitive 3D7 Plasmodium falciparum and several show promising anticancer and antimalarial activity. Although some limitations in this vector-based approach are apparent, a number of high potency Boc-protected analogues were identified with activity against malaria parasites as low as 0.21 nM. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码：2586 / 2597
页数：12
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