Mitochondrial targeted rhodium(III) complexes: Synthesis, characterized and antitumor mechanism investigation

Yan-Bo Peng; Can Tao; Cai-Ping Tan; Ping Zhao

doi:10.1016/j.jinorgbio.2021.111400

Mitochondrial targeted rhodium(III) complexes: Synthesis, characterized and antitumor mechanism investigation

J Inorg Biochem. 2021 May:218:111400. doi: 10.1016/j.jinorgbio.2021.111400. Epub 2021 Feb 25.

Authors

Yan-Bo Peng¹, Can Tao¹, Cai-Ping Tan², Ping Zhao³

Affiliations

¹ School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Education Mega Centre, No. 280, Waihuandong Road, Guangzhou 510006, PR China.
² MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, PR China. Electronic address: tancaip@mail.sysu.edu.cn.
³ School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Education Mega Centre, No. 280, Waihuandong Road, Guangzhou 510006, PR China. Electronic address: zhaoping666@163.com.

PMID: 33684684
DOI: 10.1016/j.jinorgbio.2021.111400

Abstract

Recently, rhodium complexes have received intensive attentions due to their tunable chemical and biological properties as well as attractive antitumor activity. In this work, two imidazole triphenylamino rhodium complexes [Rh(ppy)₂L1]PF6 (Rh1) and [Rh(ppy)₂L2]PF6 (Rh2) (ppy = 2-phenylpyridine, L1 = 4-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)-N,N-diphenylaniline, L2 = N-(4-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenyl)-4-methyl-N-(p-tolyl)aniline) have been synthesized and characterized. Both complexes display stronger anticancer activity against a various of cancer cells than cisplatin and they can effectively localize to mitochondria. Further mechanism studies show that Rh1 induce caspase-dependent apoptosis through mitochondrial damage, down-regulate the expression of B-cell lymphoma-2 (Bcl-2)/Bcl2-associated x (Bax) and reactive oxygen species (ROS) elevation. Our work provides a strategy for the construction of highly effective anticancer agents targeting mitochondrial metabolism through rational modification of rhodium complexes.

Keywords: Apoptosis; Mitochondrial; ROS; Rhodium complexes.

Publication types

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

MeSH terms

Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis*
Cell Proliferation
Coordination Complexes / chemistry
Coordination Complexes / pharmacology*
Humans
Mitochondria / drug effects*
Mitochondria / metabolism
Mitochondria / pathology
Molecular Structure
Neoplasms / drug therapy*
Neoplasms / metabolism
Neoplasms / pathology
Reactive Oxygen Species / metabolism*
Rhodium / chemistry*
Structure-Activity Relationship
Tumor Cells, Cultured
bcl-2-Associated X Protein / genetics
bcl-2-Associated X Protein / metabolism

Substances

Antineoplastic Agents
BAX protein, human
Coordination Complexes
Reactive Oxygen Species
bcl-2-Associated X Protein
Rhodium