C7 桥接单羰基姜黄素类似物 (MCA) 的毒性与连接酮类型之间的构效关系 (SAR) 尚不清楚。为了追求有效且细胞毒性较小的化疗药物，我们使用 C7 桥联 MCA 的各种双烯酮骨架进行了 SAR 分析，合成了含有已鉴定的低毒性环戊酮支架和邻甲氧基苯基的环状 C7 桥联 MCA，并评估了它们的抗胃癌活性和安全性。大多数化合物对胃癌细胞表现出有效的细胞毒活性。我们通过随机森林方法建立了定量构效关系模型（R2 > 0.82），为优化结构提供了重要信息。优化的化合物 2 部分通过抑制 AKT 和 STAT3 途径表现出体外和体内抗胃癌活性，并表现出良好的体内安全性。总之，本文提供了一类有前途的 MCA 和用于化疗药物开发的潜在化合物。

The structure-activity relationship (SAR) between toxicity and the types of linking ketones of C7 bridged monocarbonyl curcumin analogs (MCAs) was not clear yet. In the pursuit of effective and less cytotoxic chemotherapeutics, we conducted a SAR analysis using various diketene skeletons of C7-bridged MCAs, synthesized cyclic C7-bridged MCAs containing the identified low-toxicity cyclopentanone scaffold and an o-methoxy phenyl group, and assessed their anti-gastric cancer activity and safety profile. Most compounds exhibited potent cytotoxic activities against gastric cancer cells. We developed a quantitative structure-activity relationship model (R2 > 0.82) by random Forest method, providing important information for optimizing structure. An optimized compound 2 exhibited in vitro and in vivo anti-gastric cancer activity partly through inhibiting the AKT and STAT3 pathways, and displayed a favorable in vivo safety profile. In summary, this paper provided a promising class of MCAs and a potential compound for the development of chemotherapeutic drugs.