天然产物或合成化合物中广泛存在儿茶酚类物质，如白藜芦醇、辛花脑和羟丙基对羟基异名洛酸，具有有趣的生物活性。受到它们的结构特征的启发，本研究通过克莱森重排反应设计和合成了一系列含1,3-二芳基丙烷结构的多酚化合物，共计49种。首先以50μM浓度对新合成的化合物在多种癌细胞系（PC-3、U87MG、U251、HCT116）上进行了抗增殖活性初步评估，结果指导了该系列化合物的结构活性关系研究。进一步针对七种癌细胞系进行筛选（另加入三种结肠癌细胞系COLO205、HT29和SW480），确定了两个具有前瞻性潜力的先导化合物2t和3t，其IC50值范围为8.2±0.1至19.3±1.9μM。这两种化合物还表现出对COLO205细胞系的剂量-时间依赖的良好抗增殖活性。此外，化合物2t和3t在COLO205人源异种移植肿瘤小鼠模型中显示出良好的抗肿瘤效果，其TGI值范围为38%至58%。这些结果为进一步研究该系列化合物提供了依据。版权所有©2023 Elsevier Inc.。保留所有权利。

Polyphenols such as resveratrol, honokiol and nordihydroguaiaretic acid are widely existing in nature products or synthetic compounds with interesting biological activities. Inspired by their structural feature, a total of 49 1,3-diaryl propane-based polyphenols were designed and synthesized through Claisen rearrangement reaction. New compounds were initially assessed for their anti-proliferative activities against various cancer cell lines (PC-3, U87MG, U251, HCT116) at a concentration of 50 μM, and the results guided the SAR of this series of compounds. Further screening of selected compounds against seven cancer cell lines (three additional colon cancer cell lines namely COLO205, HT29 and SW480 were chosen) led to the identification of two advanced leads 2t and 3t with IC50 values ranging from 8.2 ± 0.1 to 19.3 ± 1.9 μM. Both compounds also showed promising anti-proliferative activities against COLO205 in dose- and time-dependent manners. Furthermore, 2t and 3t exhibited good anti-tumor efficacy in COLO205 xenografted mice model with TGI values ranging from 38% to 58%. These results warrant the further investigation of this series of compounds.Copyright © 2023 Elsevier Inc. All rights reserved.