Synthesis and in vitro antiplasmodial evaluation of 4-anilino-2-trichloromethylquinazolines

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• 作者：Pierre Verhaeghe ; Nadine Azas ; Sé ; bastien Hutter ; Caroline Castera-Ducros ; Michè ; le Laget ; Auré ; lien Dumè ; tre ; Monique Gasquet ; Jean-Pierre Reboul ; Sylvain Rault ; Pascal Rathelot ; Patr
• 关键词：Quinazoline ; Trichloromethyl group ; Plasmodium falciparum ; In vitro antiplasmodial activity ; Selectivity index
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2009
• 出版时间：1 July 2009
• 年：2009
• 卷：17
• 期：13
• 页码：4313-4322
• 全文大小：325 K

文摘

To identify a new safe antiplasmodial molecular scaffold, an original series of 2-trichloromethylquinazolines, functionalized in position 4 by an alkyl- or arylamino substituent, was synthesized from 4-chloro-2-trichloromethylquinazoline 1, via a cheap, fast and efficient solvent-free operating procedure. Among the 40 molecules prepared, several exhibit a good profile with both a significant antiplasmodial activity on the W2 Plasmodium falciparum strain (IC₅₀ values: 0.4–2.2 μM) and a promising toxicological behavior regarding human cells (HepG2/W2 selectivity indexes: 40–83), compared to the antimalarial drug compounds chloroquine and doxycycline. The in vitro antitoxoplasmic and antileishmanial evaluations were conducted in parallel on the most active molecules, showing that these ones specifically display antiplasmodial properties.