DMF-DMA 催化新型乙内酰硫脲衍生物的合成、分子对接、体外、计算机设计和结合自由能研究，作为针对 EGFR 酪氨酸激酶和芳香酶细胞色素 P450 酶的抗氧化剂和抗增殖剂。
DMF-DMA catalyzed Synthesis, molecular docking, in-vitro, in-silico design, and binding free energy studies of novel thiohydantoin derivatives as antioxidant and antiproliferative agents targeting EGFR tyrosine kinase and aromatase cytochrome P450 enzyme.
发表日期：2024 Jul 05
作者：
Israa A Seliem
来源：
ANTIOXIDANTS & REDOX SIGNALING
摘要：
合成了一组新型2-硫代乙内酰脲衍生物，并在DMFDMA催化剂的5位上讨论了烯胺酮官能团，使用肼、羟胺和2-氨基苯硫酚等试剂生成吡唑、异恶唑、苯并恶氮卓。对这些新合成的化合物的抗氧化和抗增殖活性进行了评估。 2-硫代乙内酰脲清除2,2-二苯基-1-三硝苯肼自由基(DPPH•)作用的体外研究证实了2-硫代乙内酰脲具有自由基清除和抗氧化活性。合成的化合物显示出显着的抗氧化活性。使用 MTT 测定评估 2-硫代乙内酰脲对 MCF7（乳腺）和 PC3 细胞（前列腺）的体外抗肿瘤活性。与参考药物厄洛替尼相比，一些合成的化合物显示出显着至中等的抗增殖特性。其中，化合物 4a 对 MCF7 和 PC3 癌细胞系表现出有效的抗肿瘤特性，IC50 = 2.53 ± 0.09 /ml
A set of novels 2-thiohydantoin derivatives were synthesized and enaminone function was discussed at position 5 using DMFDMA catalyst which result in formation of pyrazole, isoxazole, benzoxazepine by using reagents such as hydrazine, hydroxylamine and 2-aminothiophenol. These newly synthesized compounds were evaluated for their antioxidant and antiproliferative activity. In vitro studies on the effect of 2-thiohydantoin on scavenging 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) confirmed the free radical scavenging and antioxidant activity of 2-thiohydantoin. The synthesized compounds show significant antioxidant activity. The in vitro antitumor activity of 2-thiohydantoin on MCF7 (breast) and PC3 cells (prostate) was evaluated using MTT assay. Some of the synthesized compounds show significant to moderate antiproliferative properties compared to reference drug erlotinib. Among all, compound 4a exhibit potent antitumor properties against MCF7 and PC3 cancer cell lines with IC50 = 2.53 ± 0.09 /ml & with IC50 = 3.25 ± 0.12 µg/ml respectively and has potent antioxidant activity with IC50 = 10.04 ± 0.49 µg/ml.Copyright © 2024 Elsevier Inc. All rights reserved.