Department of Biochemistry, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico.
Department of Pharmacy, Faculty of Chemistry, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
Molecules. 2024 Sep 23;29(18):4501. doi: 10.3390/molecules29184501.
is a protozoan parasite that causes Chagas disease in humans. The current antichagasic drugs nifurtimox and benznidazole have inconveniences of toxicity; therefore, the search for alternative therapeutic strategies is necessary. The present study reports the synthesis, drug-likeness predictions, and in vitro anti-trypanosome activity of a series of 14 quinazoline 2,4,6-triamine derivatives. All compounds were tested against (epimastigotes and trypomastigotes) and in HFF1 human foreskin fibroblasts. The bioassays showed that compounds - containing nitrobenzoyl substituents at 6-position of the quinazoline 2,4,6-triamine nucleus were the most potent on its antiprotozoal activity. The effect was observed at 24 h and it was preserved for at least 5 days. Also, compounds - were not toxic to the human control cells, showing high selectivity index. The quinazoline nitro derivatives have potential use as antichagasic agents.
克氏锥虫是一种原生动物寄生虫，可导致人类恰加斯病。目前的抗恰加斯病药物硝呋替莫和苯并硝唑具有毒性方面的不便；因此，有必要寻找替代的治疗策略。本研究报告了一系列 14 种喹唑啉 2,4,6-三胺衍生物的合成、药物相似性预测和体外抗锥虫活性。所有化合物均针对 （滋养体和鞭毛体）和人包皮成纤维细胞（HFF1）进行了测试。生物测定结果表明，含有硝基苯甲酰取代基的喹唑啉 2,4,6-三胺核的化合物 - 在抗原生动物活性方面最为有效。这种作用在 24 小时内显现，并至少持续 5 天。此外，化合物 - 对人对照细胞没有毒性，显示出高选择性指数。喹唑啉硝基衍生物具有作为抗恰加斯病药物的潜力。
