本研究报告了 13 种苯并二氧戊环衍生物的设计、合成和综合生物学评价，这些衍生物源自胡椒碱的核心结构，胡椒碱是一种具有明确抗肿瘤特性的天然产物。胡椒碱主要存在于黑胡椒中，因其多种药理活性而闻名，包括抗炎、抗氧化和抗癌作用。利用胡椒碱的抗肿瘤潜力，我们旨在通过结构修饰来增强其功效。在合成的化合物中，HJ1 是最有效的，与胡椒碱相比，对 HeLa 和 MDA-MB-231 细胞系的抑制作用分别增加了 4 倍和 10 倍。此外，HJ1 表现出良好的安全性，其特点是对人类正常细胞系 293T 的细胞毒性显着降低。机制研究表明，HJ1 显着抑制 HeLa 细胞的克隆形成、迁移和粘附。利用鸡胚绒毛尿囊膜 (CAM) 模型的体内研究证实了 HJ1 强大的抗肿瘤活性，其抑制肿瘤血管生成和减轻肿瘤重量的能力就证明了这一点。这些结果表明，HJ1 作为开发新型抗肿瘤疗法的先导化合物具有重大前景。版权所有 © 2024。由 Elsevier Ltd 出版。

This study reports the design, synthesis, and comprehensive biological evaluation of 13 benzodioxolane derivatives, derived from the core structure of piperine, a natural product with established antitumor properties. Piperine, primarily found in black pepper, has been noted for its diverse pharmacological activities, including anti-inflammatory, antioxidant, and anticancer effects. Leveraging piperine's antitumor potential, we aimed to enhance its efficacy through structural modifications. Among the synthesized compounds, HJ1 emerged as the most potent, exhibiting a 4-fold and 10-fold increase in inhibitory effects on HeLa and MDA-MB-231 cell lines, respectively, compared to piperine. Furthermore, HJ1 demonstrated a favorable safety profile, characterized by significantly lower cytotoxicity towards the human normal cell line 293T. Mechanistic investigations revealed that HJ1 markedly inhibited clonogenicity, migration, and adhesion of HeLa cells. In vivo studies utilizing the chick embryo chorioallantoic membrane (CAM) model substantiated the robust antitumor activity of HJ1, evidenced by its ability to suppress tumor angiogenesis and reduce tumor weight. These results suggest that HJ1 holds significant promise as a lead compound for the development of novel antitumor therapies.Copyright © 2024. Published by Elsevier Ltd.