Here, we have identified the interaction site of the contraceptive drug gamendazole using computational modeling. The drug was previously described as a ligand for eukaryotic translation elongation factor 1-α 1 (eEF1A1) and found to be a potential target site for derivatives of 2-phenyl-3-hydroxy-4(1H)-quinolinones (3-HQs), which exhibit anticancer activity. The interaction of this class of derivatives of 3-HQs with eEF1A1 inside cancer cells was confirmed via pull-down assay. We designed and synthesized a new family of 3-HQs and subsequently applied isothermal titration calorimetry to show that these compounds strongly bind to eEF1A1. Further, we found that some of these derivatives possess significant in vitro anticancer activity.

中文翻译：

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真核翻译延伸因子1-α1 Gamendazole结合位点的绑定3-羟基-4（1 H）-喹啉酮作为新型配体具有抗癌活性。

在这里，我们使用计算模型确定了避孕药Gamendazole的相互作用部位。该药物先前被描述为真核翻译延伸因子1-α1（eEF1A1）的配体，被发现是2-苯基-3-羟基-4（1 H）-喹啉酮（3-HQs）衍生物的潜在靶位），具有抗癌活性。通过下拉测定法证实了这类3-HQs衍生物与癌细胞内eEF1A1的相互作用。我们设计并合成了一个新的3-HQ家族，随后应用了等温滴定量热法，表明这些化合物与eEF1A1牢固结合。此外，我们发现这些衍生物中的一些具有显着的体外抗癌活性。