Zhang Yirong, Yu Chuwei, Wang Linyuan, Zhou Lina, Li Chaofan, Yuan Changxian, Sun Nan, Hao Guanxiang, Ma Chenyang, Lin Yuzhe, Li Hongjing, Hong Jiali, Zhao Jinhua, Lou Kaiyan, Zhang Rui, Xie Chengying, Wang Sinan
School of Biomedical Engineering & State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai 201210, China.
School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
ACS Omega. 2025 Apr 29;10(18):18720-18732. doi: 10.1021/acsomega.5c00262. eCollection 2025 May 13.
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 , , and showed significantly enhanced antiproliferative activities on a broad scope of cancer cell lines. Further studies indicated that both and 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 . The biodistribution of compounds and 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.
异黄酮是一类具有多种生物活性的天然产物衍生的优势结构。在药物化学中，碳硼烷已被用作苯环的三维模拟物。在此，我们用碳硼烷取代了异黄酮的苯基，制备了一系列含碳硼烷的异黄酮类似物。化合物、和在广泛的癌细胞系上表现出显著增强的抗增殖活性。进一步研究表明，和均抑制JAK/STAT5、PI3K/AKT和p38 MAPK信号通路，导致G1期细胞周期阻滞。此外，这两种化合物均降低了多药耐药的关键介质P-糖蛋白（P-gp）的表达，并逆转了多药耐药细胞中化疗药物的耐药性。通过电感耦合等离子体质谱和正电子发射断层扫描成像研究评估了化合物和的生物分布。综上所述，这些结果表明含碳硼烷的异黄酮类似物具有良好的药学性质。
