Chauhan Shikha S, Sharma Moni, Chauhan Prem M S
Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow, India.
Drug News Perspect. 2010 Dec;23(10):632-46. doi: 10.1358/dnp.2010.23.10.1468390.
Artemisinin, with its 1,2,4-trioxane as active motif, is now the first-line treatment for multidrug-resistant malaria. The endoperoxide ring is essential for the antimalarial activity of artemisinin. Based on its mechanism of action, new hybrid molecules named trioxaquines with a dual mode of action have been designed. Trioxaquines are made by the covalent attachment of a trioxane, having alkylating ability, to a quinoline, known to easily penetrate within infected erythrocytes. This review discusses the importance of various hybrid molecules of artemisinin and 4-aminoquinoline in the treatment of malaria and the evolution of a trioxaquine hybrid as a promising antimalarial drug candidate.
青蒿素以其1,2,4-三氧杂环已烷作为活性基团，现已成为多重耐药疟疾的一线治疗药物。内过氧化物环对于青蒿素的抗疟活性至关重要。基于其作用机制，已设计出具有双重作用模式的新型杂合分子——三氧喹啉。三氧喹啉是通过将具有烷基化能力的三氧杂环已烷与喹啉共价连接而成，已知喹啉易于穿透受感染的红细胞。本文综述了青蒿素与4-氨基喹啉的各种杂合分子在疟疾治疗中的重要性，以及三氧喹啉杂合体作为一种有前景的抗疟候选药物的演变过程。
