2-tert-butyl-8-quinolinamines exhibit potent blood schizontocidal antimalarial activity via inhibition of heme crystallization
2-tert-butyl-8-quinolinamines exhibit potent blood schizontocidal antimalarial activity via inhibition of heme crystallization
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DOI：
10.1128/aac.00288-07
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发表时间：
2007-08-01
影响因子：
4.9
通讯作者：
Kamei, Kaeko
中科院分区：
文献类型：
--
作者：
Huy, Nguyen Tien;Mizunuma, Keisuke;Kamei, Kaeko
我们最近报道，在伯氨喹中喹啉环的C-2位置附着一个代谢稳定的大体积叔丁基，可显著提高8-喹啉胺的抗疟疾活性。由于疟原虫在血红蛋白分解代谢中释放的游离血红素是剧毒的，疟原虫主要通过将血红素结晶成不溶性的无毒血色素来保护自己。我们现在证明了2-叔丁基伯氨喹在体外抑制β -血红素形成的能力，与血红素形成1:1的复合物，并增强血红素诱导的溶血。上述结果表明，2-叔丁基伯氨喹的抗疟活性之所以显著提高，可能是由于它干扰了疟原虫的血红素分解代谢途径。
We have recently reported that the attachment of a bulky metabolically stable tert-butyl group at the C-2 position of a quinoline ring in primaquine results in a tremendous improvement in the blood schizontocidal antimalarial activity of 8-quinolinamine. Because free heme released from hemoglobin catabolism in a malarial parasite is highly toxic, the parasite protects itself mainly by crystallization of heme into insoluble nontoxic hemozoin. We now demonstrate the ability of 2-tert-butylprimaquine to inhibit in vitro beta-hematin formation, to form a complex with heme with a stoichiometry of 1:1, and to enhance heme-induced hemolysis. The results described herein indicate that a major improvement in the blood-schizontocidal antimalarial activity of 2-tert-butylprimaquine might be due to a disturbance of heme catabolism pathway in the malarial parasite.