具有与四氧杂环骨架相连的4-氨基喹啉部分的新型嵌合抗疟药。
New chimeric antimalarials with 4-aminoquinoline moiety linked to a tetraoxane skeleton.
作者信息
Opsenica Igor, Opsenica Dejan, Lanteri Charlotte Anne, Anova Lalaine, Milhous Wilbur K, Smith Kirsten S, Solaja Bogdan A
机构信息
Institute of Chemistry, Technology and Metallurgy, Belgrade, Serbia.
出版信息
J Med Chem. 2008 Oct 9;51(19):6216-9. doi: 10.1021/jm8006905. Epub 2008 Sep 6.
The synthesis of the chimeric molecules consisting of two pharmacophores, tetraoxane and 7-chloro-4-aminoquinoline, is reported. The tetraoxanes 2, 4, and 8 show relatively potent in vitro antimalarial activities, with IC90 values for the Plasmodium falciparum strain W2 of 2.26, 12.44, and 10.74 nM, respectively. In addition, two compounds, 2 and 4, cured mice in a modified Thompson test for antimalarial blood stage activity, with a minimum curative dose of 80 mg/kg, a minimum active dose of 20 mg/kg/day, and a maximum tolerated dose of >960 mg/kg.
报道了由两个药效基团四氧烷和7-氯-4-氨基喹啉组成的嵌合分子的合成。四氧烷2、4和8显示出相对较强的体外抗疟活性，恶性疟原虫W2株的IC90值分别为2.26、12.44和10.74 nM。此外，化合物2和4在改良的汤普森抗疟血期活性试验中治愈了小鼠，最小治愈剂量为80 mg/kg，最小活性剂量为20 mg/kg/天，最大耐受剂量>960 mg/kg。
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