Vladimirova Stanislava, Hristova Rossitsa, Iliev Ivan
Department of Organic Synthesis, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, Bulgaria.
Roumen Tsanev Institute of Molecular Biology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
Molecules. 2024 Nov 21;29(23):5499. doi: 10.3390/molecules29235499.
Novel pyrrole-based carbohydrazide () and hydrazones (-) were synthesized, characterized, and subjected to spectroscopic studies. The hydrazones were obtained by reacting a pyrrole hydrazide with substituted pyrrole aldehydes. The initial carbohydrazide was prepared by selective hydrazinolysis of the obtained -pyrrolylcarboxylic acid ethyl ester. The biological activity of the newly synthesized compounds was investigated in vitro on a panel of tumor and non-tumor cell lines. Mouse embryonic fibroblasts BALB 3T3 clone A31 were used in the safety test (BALB 3T3 NRU-assay). Antiproliferative activity was determined on keratinocytes (HaCaT) and melanoma (SH-4) cells by MTT dye reduction assay. The safety test of the compounds showed low cytotoxicity and absence of phototoxic potential. Among our novel pyrrole hydrazones, was the most selective (SI = 3.83) in human melanoma cells and exhibited very good antiproliferative activity (IC = 44.63 ± 3.51 μM). The cytotoxic effect of correlates with its ability to induce apoptosis and to cause cell cycle arrest in the S phase. In addition, the results show that hydrazones obtained by condensation with β-aldehydes are more bioactive than those obtained by condensation with α-aldehydes.
合成了新型吡咯基碳酰肼（）和腙（-），对其进行了表征并开展了光谱研究。通过吡咯酰肼与取代吡咯醛反应得到腙。初始碳酰肼是通过对所得到的 - 吡咯基羧酸乙酯进行选择性肼解制备的。在一组肿瘤和非肿瘤细胞系上对新合成化合物的生物活性进行了体外研究。在安全性测试中使用了小鼠胚胎成纤维细胞BALB 3T3克隆A31（BALB 3T3 NRU测定法）。通过MTT染料还原测定法对角质形成细胞（HaCaT）和黑色素瘤（SH - 4）细胞测定抗增殖活性。化合物的安全性测试显示出低细胞毒性且无光毒性潜力。在我们的新型吡咯腙中，在人黑色素瘤细胞中最具选择性（SI = 3.83），并表现出非常好的抗增殖活性（IC = 44.63 ± 3.51 μM）。的细胞毒性作用与其诱导细胞凋亡以及使细胞周期停滞在S期的能力相关。此外，结果表明，通过与β - 醛缩合得到的腙比通过与α - 醛缩合得到的腙具有更高的生物活性。
