Department of Organic Chemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Jurasza Str. 2, 85-089 Bydgoszcz, Poland.
Chair and Department of Biology and Genetics, Faculty of Pharmacy, Medical University in Lublin, Chodźki Str. 4A, 20-093 Lublin, Poland.
Molecules. 2022 Jul 13;27(14):4488. doi: 10.3390/molecules27144488.
Parasitic diseases, caused by intestinal helminths, remain a very serious problem in both human and veterinary medicine. While searching for new nematicides we examined a series of 1,2,4-triazole derivatives - obtained during reactions of -substituted amidrazones with itaconic anhydride. Two groups of compounds, - and - differed in the position of the double bond on the methacrylic acid moiety. The toxicity of derivatives - and the anti-inflammatory activity of and - were studied on peripheral blood mononuclear cells (PBMC). Antiproliferative activity of compounds and - was tested cytometrically in PBMC cultures stimulated by phytohemagglutinin. The influence of derivatives and - on the TNF-α, IL-6, IL-10 and IFN-γ production was determined by ELISA in lipopolysaccharide-stimulated PBMC cultures. Anthelmintic activity of compounds - was studied in the sp. nematodes model. Most compounds (-) proved to be non-toxic to human PBMC. Derivatives - showed anti-inflammatory activity by inhibiting the proliferation of lymphocytes. Moreover, compounds and - significantly reduced the production of TNF-α and derivatives - decreased the level of INF-γ. The strongest anti-inflammatory activity was observed for compound . Compounds and demonstrated anthelmintic activity higher than albendazole and may become promising candidates for anthelmintic drugs.
寄生虫病，由肠道蠕虫引起，在人类和兽医医学中仍然是一个非常严重的问题。在寻找新的杀线虫剂时，我们研究了一系列 1,2,4-三唑衍生物 - 由取代的 amidrazones 与衣康酸酐反应得到。两组化合物 - 和 - 在甲基丙烯酸部分的双键位置不同。衍生物 - 的毒性和 - 和 - 的抗炎活性在周围血单核细胞（PBMC）上进行了研究。在植物血凝素刺激的 PBMC 培养物中，通过细胞计量法测试化合物 和 - 的抗增殖活性。通过 ELISA 在脂多糖刺激的 PBMC 培养物中测定衍生物 和 - 对 TNF-α、IL-6、IL-10 和 IFN-γ产生的影响。在 sp. 线虫模型中研究了化合物 - 的驱虫活性。大多数化合物（-）被证明对人 PBMC 无毒。衍生物 - 通过抑制淋巴细胞增殖显示出抗炎活性。此外，化合物 和 - 显著降低了 TNF-α的产生，衍生物 - 降低了 INF-γ的水平。化合物 表现出最强的抗炎活性。化合物 和 表现出比阿苯达唑更高的驱虫活性，可能成为驱虫药物的有前途的候选药物。
