Discovery of new hit-molecules targeting Plasmodium falciparum through a global SAR study of the 4-substituted-2-trichloromethylquinazoline antiplasmodial scaffold

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• 作者：Justine Desroches^a ; ¹ ; Charline Kieffer^a ; ¹ ; Nicolas Primas^a ; Sé ; bastien Hutter^b ; Armand Gellis^a ; Hussein El-Kashef^c ; Pascal Rathelot^a ; Pierre Verhaeghe^d ; ^{pierre.verhaeghe@univ-tlse3.fr} ; Nadine Azas^b ; Patrice Vanelle^a ; ^{patrice.vanelle@univ-amu.fr}
• 关键词：Quinazoline ; Quinoline ; Quinoxaline ; Thienopyrimidine ; Trichloromethyl goup ; Plasmodium falciparum ; In vitro antiplasmodial activity ; In vitro HepG2 cytotoxicity ; Structure-activity relationships
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2017
• 出版时间：5 January 2017
• 年：2017
• 卷：125
• 期：Complete
• 页码：68-86
• 全文大小：1609 K
• 卷排序：125

文摘

Antiplasmodial pharmacomodulation of CCl3-substituted quinazolines was made. Thienopyrimidine bioisosteres appeared more cytotoxic. Two quinoxaline bioisosteres displayed in vitro IC50 values of 0.4 and 0.5 µM on the K1 multi-resistant P. falciparum strain. These quinoxalines displayed low cytotoxicity on the human HepG2 cell line (CC50 ∼ 40 µM) and improved selectivity indices (77–100).