In this work, seven acrylonitrile derivatives were selected as potential inhibitors of fat and obesity‐related proteins (FTO) by the aid of fluorescence spectroscopy, ultraviolet visible spectroscopy, molecular docking, and cytotoxicity methods. Results show that the interaction between 3‐amino‐2‐(4‐chlorophenyl)‐3‐phenylacrylonitrile (1a) and FTO was the strongest among these derivatives. Thermodynamic analysis and molecular modeling show that the main force between 1a and FTO is hydrophobic interaction. The cytotoxicity test showed that the IC₅₀ value of 1a was 46.64 μmol/L, which indicated 1a had the smallest IC₅₀ value and had the best inhibitory effect on the proliferation of leukemia K562 cells among the seven derivatives. Both our previous results and this work show that chlorine atoms play important role in the binding of small molecules and FTO. This work brings new information for the study of FTO inhibitors.

中文翻译：

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氯原子对丙烯腈衍生物与脂肪量和肥胖相关蛋白结合的作用

在这项工作中，通过荧光光谱、紫外可见光谱、分子对接和细胞毒性方法，选择了七种丙烯腈衍生物作为脂肪和肥胖相关蛋白 (FTO) 的潜在抑制剂。结果表明，在这些衍生物中，3-氨基-2-(4-氯苯基)-3-苯基丙烯腈( 1a )与FTO的相互作用最强。热力学分析和分子建模表明，1a和FTO之间的主要作用力是疏水相互作用。细胞毒性试验表明1a的IC ₅₀值为46.64 μmol/L，表明1a的IC ₅₀最小七种衍生物中对白血病K562细胞增殖的抑制作用最好。我们之前的结果和这项工作都表明氯原子在小分子和 FTO 的结合中起重要作用。这项工作为FTO抑制剂的研究带来了新的信息。