新型含吡唑并嘧啶衍生物的Rh（III）和Pd（II）配合物的体外和体内抗癌活性研究。
In vitro and in vivo anticancer activity of novel Rh(III) and Pd(II) complexes with pyrazolopyrimidine derivatives.
发表日期：2023 Sep 15
作者：
Yun-Qiong Gu, Meng-Xue Ma, Qi-Yuan Yang, Kun Yang, Huan-Qing Li, Mei-Qi Hu, Hong Liang, Zhen-Feng Chen
来源：
BIOORGANIC CHEMISTRY
摘要：
本研究合成并表征了六种吡唑嘧啶基铑(III)和钯(II)络合物分别为[Rh(L1)(H2O)Cl3] (1), [Rh(L2)(CH3OH)Cl3] (2), [Rh(L3)(H2O)Cl3] (3), [Rh2(L4)Cl6]·CH3OH (4), [Rh(L5)(CH3CN)Cl3]·0.5CH3CN (5), 和[Pd(L5)Cl2] (6)。这些络合物在六种癌细胞系中表现出高细胞毒性。大多数络合物在体外对T-24细胞的细胞毒性高于顺铂。机制研究表明，络合物5和6通过DNA损伤诱导G2/M期细胞周期停滞，并通过内质网应激反应诱导凋亡。此外，络合物5还通过线粒体功能障碍诱导细胞凋亡。络合物5和6在小鼠肿瘤模型中显示出低毒性和高抑制肿瘤生长的活性。铑络合物5对体内肿瘤生长的抑制效果比钯络合物6更明显。版权所有 © 2023 Elsevier Inc. 保留所有权利。
Six pyrazolopyrimidine rhodium(III) or palladium(II) complexes, [Rh(L1)(H2O)Cl3] (1), [Rh(L2)(CH3OH)Cl3] (2), [Rh(L3)(H2O)Cl3] (3), [Rh2(L4)Cl6]·CH3OH (4), [Rh(L5)(CH3CN)Cl3]·0.5CH3CN (5), and [Pd(L5)Cl2] (6), were synthesized and characterized. These complexes showed high cytotoxicity against six tested cancer cell lines. Most of the complexes showed higher cytotoxicity to T-24 cells in vitro than cisplatin. Mechanism studies indicated that complexes 5 and 6 induced G2/M phase cell cycle arrest through DNA damage, and induced apoptosis via endoplasmic reticulum stress response. In addition, complex 5 also induced cell apoptosis via mitochondrial dysfunction. Complexes 5 and 6 showed low in vivo toxicity and high tumor growth inhibitory activity in mouse tumor models. The inhibitory effect of rhodium complex 5 on tumor growth in vivo was more pronounced than that of palladium complex 6.Copyright © 2023 Elsevier Inc. All rights reserved.