In vitro and in vivo anticancer activity of novel Rh(III) and Pd(II) complexes with pyrazolopyrimidine derivatives

Yun-Qiong Gu; Meng-Xue Ma; Qi-Yuan Yang; Kun Yang; Huan-Qing Li; Mei-Qi Hu; Hong Liang; Zhen-Feng Chen

doi:10.1016/j.bioorg.2023.106838

In vitro and in vivo anticancer activity of novel Rh(III) and Pd(II) complexes with pyrazolopyrimidine derivatives

Bioorg Chem. 2023 Dec:141:106838. doi: 10.1016/j.bioorg.2023.106838. Epub 2023 Sep 16.

Authors

Yun-Qiong Gu¹, Meng-Xue Ma², Qi-Yuan Yang¹, Kun Yang², Huan-Qing Li², Mei-Qi Hu², Hong Liang³, Zhen-Feng Chen⁴

Affiliations

¹ State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China; School of Environment and Life Science, Nanning Normal University, Nanning 530001, China.
² State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China.
³ State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China. Electronic address: hliang@gxnu.edu.cn.
⁴ State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China. Electronic address: chenzf@gxnu.edu.cn.

PMID: 37717414
DOI: 10.1016/j.bioorg.2023.106838

Abstract

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.

Keywords: Anticancer activity; Apoptosis; Cell cycle arrest; ER-stress; Rh(III)/Pd(II) complexes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents* / metabolism
Antineoplastic Agents* / pharmacology
Apoptosis
Cell Line
Cell Line, Tumor
Coordination Complexes* / pharmacology
Mice
Neoplasms* / drug therapy
Palladium / pharmacology
Rhodium* / pharmacology

Substances

Antineoplastic Agents
Rhodium
Palladium
Coordination Complexes