具有含胺侧链的两亲性萘并噻唑鎓盐的体外和体内抗疟活性。
In vitro and in vivo antimalarial activity of amphiphilic naphthothiazolium salts with amine-bearing side chains.
机构信息
The Kenneth S. Warren Institute, Ossining, New York; University of North Carolina, Chapel Hill, North Carolina; Johns Hopkins Malaria Institute, Baltimore, Maryland.
The Kenneth S. Warren Institute, Ossining, New York; University of North Carolina, Chapel Hill, North Carolina; Johns Hopkins Malaria Institute, Baltimore, Maryland
出版信息
Am J Trop Med Hyg. 2014 Oct;91(4):824-32. doi: 10.4269/ajtmh.13-0565. Epub 2014 Sep 2.
Because of emerging resistance to existing drugs, new chemical classes of antimalarial drugs are urgently needed. We have rationally designed a library of compounds that were predicted to accumulate in the digestive vacuole and then decrystallize hemozoin by breaking the iron carboxylate bond in hemozoin. We report the synthesis of 16 naphthothiazolium salts with amine-bearing side chains and their activities against the erythrocytic stage of Plasmodium falciparum in vitro. KSWI-855, the compound with the highest efficacy against the asexual stages of P. falciparum in vitro, also had in vitro activity against P. falciparum gametocytes and in vivo activity against P. berghei in a murine malaria model.
由于现有药物的抗药性不断出现，急需开发新的抗疟药物化学类别。我们合理设计了一个化合物库，这些化合物预计会在消化液泡中积累，然后通过破坏疟原血红素中的铁羧酸盐键使疟原血红素结晶。我们报告了 16 种带有胺侧链的萘并噻唑鎓盐的合成及其对体外疟原虫红细胞阶段的活性。KSWI-855 是体外对恶性疟原虫无性生殖阶段活性最高的化合物，对恶性疟原虫配子体也有体外活性，对伯氏疟原虫在小鼠疟疾模型中也有体内活性。
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