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

页码：2586 / 2597

页数：12

共 51 条

[1] POTASSIUM FLUORIDE ON CELITE - VERSATILE REAGENT FOR C-ALKYLATION,N-ALKYLATION,O-ALKYLATION, AND S-ALKYLATION [J].

ANDO, T ;

YAMAWAKI, J .

CHEMISTRY LETTERS, 1979, (01) :45-46

[2] Artemisinin-derived sesquiterpene lactones as potential antitumour compounds: Cytotoxic action against bone marrow and tumour cells [J].

Beekman, AC ;

Wierenga, PK ;

Woerdenbag, HJ ;

Van Uden, W ;

Pras, N ;

Konings, AWT ;

El-Feraly, FS ;

Galal, AM ;

Wikstrom, HV .

PLANTA MEDICA, 1998, 64 (07) :615-619

[3] Stereochemistry-dependent cytotoxicity of some artemisinin derivatives [J].

Beekman, AC ;

Barentsen, ARW ;

Woerdenbag, HJ ;

VanUden, W ;

Pras, N ;

Konings, AWT ;

ElFeraly, FS ;

Galal, AM ;

Wikstrom, HV .

JOURNAL OF NATURAL PRODUCTS, 1997, 60 (04) :325-330

[4]

Beekman AC, 1996, PHYTOTHER RES, V10, P140, DOI 10.1002/(SICI)1099-1573(199603)10:2<140::AID-PTR792>3.0.CO

[5]

2-D

[6] THE ROLE OF CHARGE IN POLYAMINE ANALOG RECOGNITION [J].

BERGERON, RJ ;

MCMANIS, JS ;

WEIMAR, WR ;

SCHREIER, KM ;

GAO, FL ;

WU, QH ;

ORTIZOCASIO, J ;

LUCHETTA, GR ;

PORTER, C ;

VINSON, JRT .

JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (13) :2278-2285

[7] A comparison of structure-activity relationships between spermidine and spermine analogue antineoplastics [J].

Bergeron, RJ ;

Feng, Y ;

Weimar, WR ;

McManis, JS ;

Dimova, H ;

Porter, C ;

Raisler, B ;

Phanstiel, O .

JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (10) :1475-1494

[8] ARTEETHER, A NEW ANTIMALARIAL DRUG - SYNTHESIS AND ANTIMALARIAL PROPERTIES [J].

BROSSI, A ;

VENUGOPALAN, B ;

GERPE, LD ;

YEH, HJC ;

FLIPPENANDERSON, JL ;

BUCHS, P ;

LUO, XD ;

MILHOUS, W ;

PETERS, W .

JOURNAL OF MEDICINAL CHEMISTRY, 1988, 31 (03) :645-650

[9] TARGETING OF CYTOTOXIC AGENTS BY POLYAMINES - SYNTHESIS OF A CHLORAMBUCIL SPERMIDINE CONJUGATE [J].

COHEN, GM ;

CULLIS, PM ;

HARTLEY, JA ;

MATHER, A ;

SYMONS, MCR ;

WHEELHOUSE, RT .

JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1992, (04) :298-300

[10]

Cohen S.S., 1998, GUIDE POLYAMINES

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