Synthesis and Biological Evaluation of Acridine Derivatives as Antimalarial Agents
作者: Dr. Xiao‐Min YuDr. Florence RamiandrasoaDr. Lucie GuetzoyanDr. Bruno PradinesEdgar QuintinoDr. Daniele GadelleDr. Patrick ForterreDr. Thierry CresteilProf. Jean‐Pierre MahyDr. Stéphanie Pethe
作者单位: 1Université Paris‐Sud 11, Institut de Chimie Moléculaire et des Matériaux d'Orsay, Equipe de Chimie Bioorganique et Bioinorganique, Orsay 91405 CEDEX (France)
2 CNRS, UMR 8182, Orsay 91405 CEDEX (France)
3 Institut de Recherche Biomédicale des Armées, Unité de Parasitologie, Unité Mixte de Recherche 6236, Allée du Médecin Colonel Jamot, Parc du Pharo, BP 60109, Marseille 13262 CEDEX 07 (France)
4 Université Paris‐Sud 11, Institut de Génétique et Microbiologie, Orsay 91405 CEDEX (France)
5 CNRS, UMR 8621, Orsay 91405 CEDEX (France)
6 Ciblothèque cellulaire, Institut de Chimie des Substances Naturelles, CNRS, UPR 2301, Gif‐sur‐Yvette, 91198 CEDEX (France)
7 Université Paris‐Sud 11, Institut de Chimie Moléculaire et des Matériaux d'Orsay, Equipe de Chimie Bioorganique et Bioinorganique, Orsay 91405 CEDEX (France)
刊名: ChemMedChem, 2012, Vol.7 (4), pp.587-605
来源数据库: Wiley Journal
DOI: 10.1002/cmdc.201100554
关键词: aminoacridinesantiparasitic agentsmalariaPlasmodium falciparumtopoisomerasesβ‐hematin
原始语种摘要: Abstract(#br)New N ‐alkylaminoacridine derivatives attached to nitrogen heterocycles were synthesized, and their antimalarial potency was examined. They were tested in vitro against the growth of Plasmodium falciparum , including chloroquine (CQ)‐susceptible and CQ‐resistant strains. This biological evaluation has shown that the presence of a heterocyclic ring significantly increases the activity against P. falciparum . The best compound shows a nanomolar IC50 value toward parasite proliferation on both CQ‐susceptible and CQ‐resistant strains. The antimalarial activity of these new acridine derivatives can be explained by the two mechanisms studied in this work. First, we showed the capacity of these compounds to inhibit heme biocrystallization, a detoxification process...
全文获取路径: Wiley  (合作)
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关键词翻译
关键词翻译
  • parasite 寄生物
  • malaria 疟疾
  • chloroquine 氯奎
  • antiparasitic 抗蠕虫药
  • antimalarial 抗疟药
  • hematin 正铁血红素
  • essential 本质的
  • inhibitory 禁止的
  • resistant 耐久的
  • activity 活度