Bernardo Leandro B, Vieira Leandro A, Borges Caio V N, Buitrago Pedro A G, Kuča Kamil, França Tanos C C, Cavalcante Samir F A, Sousa Roberto B, Lima Antônio L S, Kitagawa Daniel A S
Military Institute of Engineering (IME), Praça General Tibúrcio 80, Rio de Janeiro-RJ, 22290-270, Brazil.
Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN), Brazilian Army Technological Center (Ctex), Av. das Américas 28705, Área 4, Rio de Janeiro-RJ, 23020-470, Brazil.
Arch Toxicol. 2025 May;99(5):2225-2228. doi: 10.1007/s00204-025-03976-7. Epub 2025 Mar 4.
Recent events involving nerve agents of the A-Series, a once elusive class of chemical warfare agents, have provoked a great concern in the international community. In this paper, continuing our research efforts in Medicinal Chemistry at the Brazilian Institute of Chemical, Biological, Radiological and Nuclear Defense (IDQBRN) (an OPCW-designated Laboratory for environmental samples), we explore ANMP, an A-230 surrogate, in the search for new treatment options for intoxications caused by these chemicals. Five isatin-pyridine oxime hybrids were evaluated as acetylcholinesterase (AChE) reactivators using a modified Ellman's assay. Our results indicate that monocationic hybrids with five methylene units, as well as its oxa-analog, are promising compounds for the design of new AChE reactivators.
近期涉及A系列神经毒剂（一类曾经难以捉摸的化学战剂）的事件引起了国际社会的高度关注。在本文中，我们继续在巴西化学、生物、放射和核防御研究所（IDQBRN）（一个被禁止化学武器组织指定的环境样本实验室）开展药物化学研究工作，探索A-230替代物ANMP，以寻找针对这些化学品中毒的新治疗方案。使用改良的Ellman测定法评估了五种异吲哚啉-吡啶肟杂化物作为乙酰胆碱酯酶（AChE）复活剂的效果。我们的结果表明，具有五个亚甲基单元的单阳离子杂化物及其氧类似物是设计新型AChE复活剂的有前景的化合物。
