Centro de Biociências, Programa de Pós-graduação em Morfotecnologia, Universidade Federal de Pernambuco, Recife, Brazil.
Departamento de Antibióticos, Universidade Federal de Pernambuco, Av. Prof. Moraes Rego, 1235 - Cidade Universitária, CEP 50.670-901, Recife, PE, Brazil.
Acta Trop. 2023 Sep;245:106965. doi: 10.1016/j.actatropica.2023.106965. Epub 2023 Jun 7.
The present work aimed to carry out in vitro biological assays of thiazole compounds against adult worms of Schistosoma mansoni, as well as the in silico determination of pharmacokinetic parameters to predict the oral bioavailability of these compounds. In addition to presenting moderate to low cytotoxicity against mammalian cells, thiazole compounds are not considered hemolytic. All compounds were initially tested at concentrations ranging from 200 to 6.25 μM against adult worms of S. mansoni parasites. The results showed the best activity of PBT2 and PBT5 at a concentration of 200 μM, which caused 100% mortality after 3 h of incubation. While at 6 h of exposure, 100% mortality was observed at the concentration of 100 µM. Subsequent studies with these same compounds allowed classifying PBT5, PBT2, PBT6 and PBT3 compounds, which were considered active and PBT1 and PBT4 compounds, which were considered inactive. In the ultrastructural analysis the compounds PBT2 and PBT5 (200 µM) promoted integumentary changes with exposure of the muscles, formation of integumentary blisters, integuments with abnormal morphology and destruction of tubercles and spicules. Therefore, the compounds PBT2 and PBT5 are promising antiparasitics against S. mansoni.
本工作旨在对噻唑类化合物进行抗曼氏血吸虫成虫的体外生物学检测，并通过计算预测这些化合物的口服生物利用度的药代动力学参数。噻唑类化合物除了对哺乳动物细胞具有中等至低毒性外，还不具有溶血作用。所有化合物最初在 200 至 6.25 μM 的浓度下对曼氏血吸虫寄生虫的成虫进行测试。结果表明，PBT2 和 PBT5 在 200 μM 浓度下表现出最佳活性，孵育 3 小时后可导致 100%的死亡率。而在暴露 6 小时时，100 μM 浓度下可观察到 100%的死亡率。对这些相同化合物的后续研究将 PBT5、PBT2、PBT6 和 PBT3 化合物归类为活性化合物，而 PBT1 和 PBT4 化合物归类为非活性化合物。在超微结构分析中，化合物 PBT2 和 PBT5（200 μM）在暴露于肌肉时可引起表皮变化、形成表皮水疱、表皮形态异常和破坏结节和刺。因此，化合物 PBT2 和 PBT5 是对抗曼氏血吸虫的有前途的抗寄生虫药物。
