Synthesis, antimalarial, antileishmanial, antimicrobial, cytotoxicity, and methemoglobin (MetHB) formation activities of new 8-quinolinamines
Synthesis, antimalarial, antileishmanial, antimicrobial, cytotoxicity, and methemoglobin (MetHB) formation activities of new 8-quinolinamines
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DOI：
10.1016/j.bmc.2006.10.036
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发表时间：
2007-01-15
影响因子：
3.5
通讯作者：
Jain, Rahul
中科院分区：
文献类型：
--
作者：
Kaur, Kirandeep;Patel, Sanjay R.;Jain, Rahul
我们报告的合成，在体外抗原动物（对疟原虫和利什曼原虫），抗菌，细胞毒性（Vero和MetHb生产性能），并在体内抗疟活性的两个系列的8-喹啉胺。以6-甲氧基-8-硝基喹啉和4-甲氧基-2-硝基-5-戊氧基苯胺为原料，经六步反应合成了N 1-{4-[2-（叔丁基）-6-甲氧基-8-喹啉氨基]戊基}-（2S/2 R）-2-氨基取代酰胺（21-33）和NI -[4-（4-乙基-6-甲氧基-5-戊氧基-8-喹啉氨基）戊基]-（2S/2 R）-2-氨基取代酰胺（51-63）。几种类似物显示出有前途的抗疟活性，在体外对恶性疟原虫D 6（氯喹敏感）和W2（氯喹抗性）克隆与哺乳动物细胞的高选择性指数。最有希望的类似物（21-24）在伯氏疟原虫感染的小鼠模型中也显示出有效的体内抗疟活性。最有趣的是，许多类似物表现出有前途的体外抗杜氏利什曼原虫前鞭毛体的抗利什曼原虫活性，以及对一组致病性细菌和真菌的抗菌活性。几种类似物，特别是21 - 24、26-32和60，与伯氨喹相比显示出较少的MetHb形成，表明这些化合物在基于8-喹啉胺的抗疟药物开发中的潜力。(c)2006爱思唯尔有限公司保留所有权利。
We report the synthesis, in vitro antiprotozoal (against Plasmodium and Leishmania), antimicrobial, cytotoxicity (Vero and MetHb-producing properties), and in vivo antimalarial activities of two series of 8-quinolinamines. N1-{4-[2-(tert-Butyl)-6-methoxy-8-quinolylamino]pentyl}-(2S/2R)-2-aminosubstitutedamides (21-33) and NI -[4-(4-ethyl-6-methoxy-5-pentyloxy-8-quinolylamino)pentyl]-(2S/2R)-2-aminosubstitutedamides (51-63) were synthesized in six steps from 6-methoxy-8-nitroquinoline and 4-methoxy-2-nitro5-pentyloxyaniline, respectively. Several analogs displayed promising antimalarial activity in vitro against Plasmodium falciparum D6 (chloroquine-senitive) and W2 (chloroquine-resistant) clones with high selectivity indices versus mammalian cells. The most promising analogs (21-24) also displayed potent antimalarial activity in vivo in a Plasmodium berghei-infected mouse model. Most interestingly, many analogs exhibited promising in vitro antileishmanial activity against Leishmania donovani promastigotes, and antimicrobial activities against a panel of pathogenic bacteria and fungi. Several analogs, notably 21 24, 26-32, and 60, showed less MetHb formation compared to primaquine indicating the potential of these compounds in 8-quinolinamine-based antimalarial drug development. (c) 2006 Elsevier Ltd. All rights reserved.