Šermukšnytė Aida, Kantminienė Kristina, Jonuškienė Ilona, Tumosienė Ingrida, Petrikaitė Vilma
Department of Organic Chemistry, Kaunas University of Technology, Radvilėnų pl. 19, 50254 Kaunas, Lithuania.
Department of Physical and Inorganic Chemistry, Kaunas University of Technology, Radvilėnų pl. 19, 50254 Kaunas, Lithuania.
Pharmaceuticals (Basel). 2022 Aug 20;15(8):1026. doi: 10.3390/ph15081026.
4-Phenyl-3-[2-(phenylamino)ethyl]-1-1,2,4-triazole-5(4)-thione was used as a starting compound for the synthesis of the corresponding 1,2,4-triazol-3-ylthioacetohydrazide, which reacts with isatins and various aldehydes bearing aromatic and heterocyclic moieties provided target hydrazones. Their cytotoxicity was tested by the MTT assay against human melanoma IGR39, human triple-negative breast cancer (MDA-MB-231), and pancreatic carcinoma (Panc-1) cell lines. The selectivity of compounds towards cancer cells was also studied. In general, the synthesized compounds were more cytotoxic against the melanoma cell line. '-(2-oxoindolin-3-ylidene)-2-((4-phenyl-5-(2-(phenylamino)ethyl)-4-1,2,4-triazol-3-yl)thio)acetohydrazide, '-((1-pyrrol-2-yl)methylene)-2-((4-phenyl-5-(2-(phenylamino)ethyl)-4-1,2,4-triazol-3-yl)thio)acetohydrazide and '-(2-hydroxy-5-nitrobenzylidene)-2-((4-phenyl-5-(2-(phenylamino)ethyl)-4-1,2,4-triazol-3-yl)thio)acetohydrazide were identified as the most active among all synthesized compounds in 3D cell cultures. '-(4-(dimethylamino)benzylidene)-2-((4-phenyl-5-(2-(phenylamino)ethyl)-4-1,2,4-triazol-3-yl)thio)acetohydrazide inhibited all cancer cell migration, was characterized as relatively more selective towards cancer cells, and could be further tested as an antimetastatic candidate.
4-苯基-3-[2-(苯基氨基)乙基]-1,2,4-三唑-5(4)-硫酮被用作合成相应的1,2,4-三唑-3-基硫代乙酰肼的起始化合物，该化合物与异吲哚酮以及带有芳族和杂环部分的各种醛反应生成目标腙。通过MTT法测试了它们对人黑色素瘤IGR39、人三阴性乳腺癌（MDA-MB-231）和胰腺癌（Panc-1）细胞系的细胞毒性。还研究了化合物对癌细胞的选择性。一般来说，合成的化合物对黑色素瘤细胞系的细胞毒性更大。α-(2-氧代吲哚啉-3-亚基)-2-((4-苯基-5-(2-(苯基氨基)乙基)-4H-1,2,4-三唑-3-基)硫代)乙酰肼、α-((1-吡咯-2-基)亚甲基)-2-((4-苯基-5-(2-(苯基氨基)乙基)-4H-1,2,4-三唑-3-基)硫代)乙酰肼和α-(2-羟基-5-硝基亚苄基)-2-((4-苯基-5-(2-(苯基氨基)乙基)-4H-1,2,4-三唑-3-基)硫代)乙酰肼被确定为3D细胞培养中所有合成化合物中活性最高的。α-(4-(二甲基氨基)亚苄基)-2-((4-苯基-5-(2-(苯基氨基)乙基)-4H-1,2,4-三唑-3-基)硫代)乙酰肼抑制所有癌细胞迁移，对癌细胞表现出相对更高的选择性，可作为抗转移候选物进一步测试。
