Synthesis and Anticancer Activity Evaluation of Novel Carborane-Containing Isoflavonoid Analogues

作者：Yirong Zhang, Chuwei Yu, Linyuan Wang, Lina Zhou, Chaofan Li, Changxian Yuan, Nan Sun, Guangzhou Hao, Chenyang Ma, Yuzhe Lin, Hongjing Li, Jiali Hong, Jinhua Zhao, Kaiyan Lou, Rui Zhang, Chengying Xie, Sinan Wang · 发表于：ACS Omega · 年份：2025 · DOI：10.1021/acsomega.5c00262 · 被引用次数：3 · 研究领域：Boron Compounds in Chemistry、Radiopharmaceutical Chemistry and Applications、Medical Imaging Techniques and Applications

High Resolution Image Download MS PowerPoint Slide Isoflavonoids represent a privileged structure derived from natural products with diverse bioactivities. Carborane has been utilized as a three-dimensional mimetic of phenyl rings in medicinal chemistry. Herein, we replaced the phenyl group of isoflavonoids with carborane and prepared a series of carborane-containing isoflavonoid analogues. Compounds 1d, 1g, and 1m showed significantly enhanced antiproliferative activities on a broad scope of cancer cell lines. Further studies indicated that both 1d and 1m inhibited JAK/STAT5, PI3K/AKT, and p38 MAPK pathways, leading to G1 cell cycle phase arrest. Additionally, both compounds reduced the expression of P-glycoprotein (P-gp), a key mediator in multidrug resistance, and reversed the resistance of chemotherapeutic agents in multidrug-resistant cells in vitro . The biodistribution of compounds 1d and 1m was evaluated through ICP-mass and positron emission tomography imaging studies. Taken together, these results suggested promising pharmaceutical properties for the carborane-containing isoflavonoid analogues.