Anti-Plasmodium activity of imidazole-dioxolane compounds

被引：33
作者：
Vlahakis, JZ
Kinobe, RT
Nakatsu, K
Szarek, WA
Crandall, IE
机构：
[1] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada
[2] Queens Univ, Dept Chem, Kingston, ON K7L 3N6, Canada
[3] Queens Univ, Dept Pharmacol & Toxicol, Kingston, ON K7L 3N6, Canada
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 09期
基金：
加拿大健康研究院;
关键词：
antimalarial; Plasmodium falciparum; imidazole-dioxolane compounds;
D O I：
10.1016/j.bmcl.2006.01.122
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of imidazole-dioxolane compounds, which we hypothesize should bind to heme and thus interfere with heme catabolism in the parasite, were assayed for inhibitory activity in Plasmodium falciparum cultures and the results were compared to those obtained with Chinese hamster ovary (CHO) cells. The majority of the compounds displayed a similar ratio of inhibitory activity in the two culture systems; however, a number of the compounds tested showed promising anti-Plasmodium activity. The mechanism of action of these compounds remains unclear, however their inability to act synergistically with chloroquine suggests that, if they are inhibiting heme detoxification, they do so in a manner that does not complement the action of chloroquine. (C) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码：2396 / 2406
页数：11
相关论文
共 38 条
[1]   Oxidative stress in malaria parasite-infected erythrocytes: host-parasite interactions [J].
Becker, K ;
Tilley, L ;
Vennerstrom, JL ;
Roberts, D ;
Rogerson, S ;
Ginsburg, H .
INTERNATIONAL JOURNAL FOR PARASITOLOGY, 2004, 34 (02) :163-189
[2]   Antimalarial chemotherapy: young guns or back to the future? [J].
Biagini, GA ;
O'Neill, PM ;
Nzila, A ;
Ward, SA ;
Bray, PG .
TRENDS IN PARASITOLOGY, 2003, 19 (11) :479-487
[3]   Access to hematin: The basis of chloroquine resistance [J].
Bray, PG ;
Mungthin, M ;
Ridley, RG ;
Ward, SA .
MOLECULAR PHARMACOLOGY, 1998, 54 (01) :170-179
[4]   USE OF THE MTT ASSAY FOR RAPID-DETERMINATION OF CHEMOSENSITIVITY OF HUMAN-LEUKEMIC BLAST CELLS [J].
CAMPLING, BG ;
PYM, J ;
GALBRAITH, PR ;
COLE, SPC .
LEUKEMIA RESEARCH, 1988, 12 (10) :823-&
[5]   Inhibition of heme crystal growth by antimalarials and other compounds: implications for drug discovery [J].
Chong, CR ;
Sullivan, DJ .
BIOCHEMICAL PHARMACOLOGY, 2003, 66 (11) :2201-2212
[6]   MALARIAL HAEMOZOIN BETA-HEMATIN SUPPORTS HEME POLYMERIZATION IN THE ABSENCE OF PROTEIN [J].
DORN, A ;
STOFFEL, R ;
MATILE, H ;
BUBENDORF, A ;
RIDLEY, RG .
NATURE, 1995, 374 (6519) :269-271
[7]  
ECKMAN JR, 1977, J LAB CLIN MED, V90, P767
[8]   Inhibitory activity of human lactoferrin and its peptide on chondroitin sulfate A-, CD36-, and thrombospondin-mediated cytoadherence of Plasmodium falciparum-infected erythrocytes [J].
Eda, S ;
Eda, K ;
Prudhomme, JG ;
Sherman, IW .
BLOOD, 1999, 94 (01) :326-332
[9]   Fate of haem iron in the malaria parasite Plasmodium falciparum [J].
Egan, TJ ;
Combrinck, JM ;
Egan, J ;
Hearne, GR ;
Marques, HM ;
Ntenteni, S ;
Sewell, BT ;
Smith, PJ ;
Taylor, D ;
van Schalkwyk, DA ;
Walden, JC .
BIOCHEMICAL JOURNAL, 2002, 365 :343-347
[10]   The treatment of Plasmodium falciparum-infected erythrocytes with chloroquine leads to accumulation of ferriprotoporphyrin IX bound to particular parasite proteins and to the inhibition of the parasite's 6-phosphogluconate dehydrogenase [J].
Famin, O ;
Ginsburg, H .
PARASITE, 2003, 10 (01) :39-50
1234