INHIBITION OF TRYPANOSOMA CRUZI GROWTH IN MAMMALIAN CELLS BY NIMODIPINE, WITH LOW CYTOTOXICITY TO HOST CELLS

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著者

    • HIROTA KENICHIRO
    • Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine
    • TSUBOUCHI AKIKO
    • Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine
    • NARA TAKESHI
    • Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine
    • AOKI TAKASHI
    • Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine

抄録

An in vitro infection system of <I>Trypanosoma cruzi</I> and HeLa cells was used to measure the anti-<I>T. cruzi</I> activities of various calcium antagonists classified into dihydropyridines, diphenylalkylamines, and benzothiazepines and of allopurinol and benznidazole as medium and highly effective reference compounds, respectively. Six dihydropyridines (10 μM each), i. e. nifedipine, nicardipine, nimodipine, nisoldipine, nitrendipine, and amlodipine, decreased the rates of infection of HeLa cells from 11.7% (control) to 5.8, 0.9, 1.2, 3.6, 5.9, and 1.7%, respectively. Nicardipine and amlodipine were highly toxic to HeLa cells, causing detachment of cells from coverslips. Nimodipine was thus the most effective inhibitor tested against <I>T. cruzi</I> infection in HeLa cells. Verapamil and gallopamil (diphenylalkylamines), diltiazem and midazolam (benzothiazepines), and allopurinol (positive control) were less effective than nimodipine. IC<SUB>50</SUB> values, the concentrations of compounds that elicited a 50% reduction in the infection rates of HeLa cells, were 2.5, 2.6, 1.3, 2.1, and 1.7 μM for nicardipine, nimodipine, amlodipine, verapamil, and benznidazole, respectively, while the values for nifedipine, diltiazem, and allopurinol were much higher. Nicardipine, amlodipine, and verapamil again showed significant cytotoxicities to HeLa cells. When Swiss 3T3 fibroblasts replaced HeLa cells, nimodipine markedly lowered the host-cell-infection rate, with an IC<SUB>50</SUB> value of 8.3 nM. Thus, nimodipine is expected to be a highly effective anti-<I>T. cruzi</I> lead compound, with low cytotoxicity to mammalian cells. Structural formulas of nimodipine and nicardipine in relation to their low and high cytotoxicities, respectively, against HeLa cells are discussed.

収録刊行物

  • Tropical medicine and health

    Tropical medicine and health 32(2), 181-188, 2004-06-01

    日本熱帯医学会

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被引用文献:  1件中 1-1件 を表示

各種コード

  • NII論文ID(NAID)
    10013297272
  • NII書誌ID(NCID)
    AA11912846
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    13488945
  • データ提供元
    CJP書誌  CJP引用  J-STAGE 
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