Chalcone is a privileged structure, demonstrating promising anti-inflammatory and anticancer activities. One potential mechanism is to suppress nuclear factor kappa B (NF-κB) activation. The structures of chalcone-based NF-κB inhibitors vary significantly that there is minimum information about their structure−activity relationships (SAR). This study aims to establish SAR of chalcone-based compounds to NF-κB inhibition, to explore the feasibility of developing simple chalcone-based potent NF-κB inhibitors, and to evaluate their anticancer activities. Three series of chalcones were synthesized in one to three steps with the key step being aldol condensation. These candidates demonstrated a wide range of NF-κB inhibitory activities, some of low micromolar potency, establishing that structural complexity is not required for NF-κB inhibition. Lead compounds also demonstrate potent cytotoxicity against lung cancer cells. Their cytotoxicities correlate moderately well with their NF-κB inhibitory activities, suggesting that suppressing NF-κB activation is likely responsible for at least some of the cytotoxicities. One lead compound effectively inhibits lung tumor growth with no signs of adverse side effects.

中文翻译：

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查尔酮导致 3-Hydroxy-4,3',4',5'-四甲氧基查耳酮及其类似物作为强效核因子 κB 抑制剂的构效关系研究及其抗癌活性

查尔酮是一种特殊的结构，具有很好的抗炎和抗癌活性。一种潜在的机制是抑制核因子 kappa B (NF-κB) 的激活。基于查尔酮的 NF-κB 抑制剂的结构差异很大，以至于关于它们的构效关系 (SAR) 的信息很少。本研究旨在建立查尔酮类化合物对 NF-κB 抑制作用的 SAR，探索开发简单的查尔酮类强效 NF-κB 抑制剂的可行性，并评估其抗癌活性。三个系列的查耳酮通过一到三个步骤合成，其中关键步骤是醛醇缩合。这些候选物表现出广泛的 NF-κB 抑制活性，一些低微摩尔效力，确定结构复杂性不是 NF-κB 抑制所必需的。先导化合物还表现出对肺癌细胞的有效细胞毒性。它们的细胞毒性与其 NF-κB 抑制活性适度相关，这表明抑制 NF-κB 活化可能是至少部分细胞毒性的原因。一种先导化合物可有效抑制肺肿瘤的生长，且没有不良副作用的迹象。