Centro de Biotecnología Genómica, Instituto Politécnico Nacional, 88710, Reynosa, México.
Med Chem. 2012 Nov;8(6):1039-44. doi: 10.2174/1573406411208061039.
Chagas disease continues to be one of the main parasitic diseases in Latin America. Despite the fact that it was discovered more than 100 years ago, no suitable pharmacologic treatment is available. We report the synthesis of new sulfonamidoquinoline and sulfonamides derivatives that were evaluated in vitro against two strains of Trypanosoma cruzi (NINOA and INC-5). Structure-activity relationship analysis indicated that small aromatic and large aromatic substituents on 4-aminoquinaldine increased trypanocidal activity on INC-5 and NINOA strains, respectively. Additionally, results show the importance of the sulfonamide group as a scaffold for the development of new anti-T. cruzi agents. Seven sulfonamide derivatives showed better lytic activity than nifurtimox and beznidazole against both strains of T. cruzi. N- (biphenyl-4-yl-sulfonyl)-nicotinamide (P-012) was established as the leader of the series for the development of more effective agents.
恰加斯病仍然是拉丁美洲的主要寄生虫病之一。尽管它在 100 多年前就被发现了，但目前还没有合适的药物治疗方法。我们报告了新的磺酰胺喹啉和磺酰胺衍生物的合成，这些衍生物在体外对两种克氏锥虫（NINOA 和 INC-5）株进行了评估。构效关系分析表明，4-氨基喹啉上的小芳香和大芳香取代基分别增加了对 INC-5 和 NINOA 株的杀锥虫活性。此外，结果表明磺酰胺基作为开发新的抗克氏锥虫药物的支架的重要性。七种磺酰胺衍生物对两种克氏锥虫株的裂解活性均优于硝呋替莫和贝那唑嗪。N-（联苯-4-基-磺酰基）-烟酰胺（P-012）被确定为该系列中开发更有效药物的先导化合物。
