Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S. A. S. Nagar, Punjab 160 062, India.
Bioorg Med Chem. 2011 Jan 1;19(1):197-210. doi: 10.1016/j.bmc.2010.11.036. Epub 2010 Nov 25.
In continuing our search of potent antimalarials based on 8-aminoquinoline structural framework, three series of novel bis(8-aminoquinolines) using convenient one to four steps synthetic procedures were synthesized. The bisquinolines were evaluated for in vitro antimalarial (Plasmodiumfalciparum), antileishmanial (Leishmaniadonovani), antimicrobial (a panel of pathogenic bacteria and fungi), cytotoxicity, β-hematin inhibitory and methemoglobin (MetHb) formation activities. Several compounds exhibited superior antimalarial activities compared to parent drug primaquine. Selected compounds (44, 61 and 79) when tested for in vivo blood-schizontocidal antimalarial activity (Plasmodiumberghei) displayed potent blood-schizontocial activities. The bisquinolines showed negligible MetHb formation (0.2-1.2%) underlining their potential in the treatment of glucose-6-phosphate dehydrogenase deficient patients. The bisquinoline analogues (36, 73 and 79) also exhibited promising in vitro antileishmanial activity, and antimicrobial activities (43, 44 and 76) against a panel of pathogenic bacteria and fungi. The results of this study provide evidence that bis(8-aminoquinolines), like their bis(4-aminoquinolines) and artemisinin dimers counterparts, are a promising class of antimalarial agents.
在继续基于 8-氨基喹啉结构框架寻找有效抗疟药物的过程中，我们采用方便的一至四步合成方法合成了三系列新型双（8-氨基喹啉）。对双喹啉进行了体外抗疟（恶性疟原虫）、抗利什曼原虫（利什曼原虫）、抗菌（一组致病性细菌和真菌）、细胞毒性、β-血红素抑制和高铁血红蛋白（MetHb）形成活性的评估。与母体药物伯氨喹相比，几种化合物表现出优异的抗疟活性。当测试体内血裂殖体抗疟活性（疟原虫伯氏疟原虫）时，选定的化合物（44、61 和 79）表现出有效的血裂殖体活性。双喹啉在体内形成的高铁血红蛋白（MetHb）很少（0.2-1.2%），这表明它们在治疗葡萄糖-6-磷酸脱氢酶缺乏症患者方面具有潜力。双喹啉类似物（36、73 和 79）还表现出有希望的体外抗利什曼原虫活性，以及对一组致病性细菌和真菌的抗菌活性（43、44 和 76）。这项研究的结果表明，双（8-氨基喹啉）与双（4-氨基喹啉）和青蒿素二聚体类似物一样，是一类很有前途的抗疟药物。
