A Rhein-Based Rh(Ⅲ) Arene Complex with Anti-tumor Cell Proliferative Activity Inhibits RNA Demethylase FTO  

作　　者：Lu Liu Yaqiong Kong Liang He Xiuxiu Wang Meng-Meng Wang Hongjiao Xu Cai-Guang Yang Zhi Su Jing Zhao Zong-Wan Mao Yue Huang Hong-Ke Liu 

机构地区：[1]School of Chemistry and Materials Science,Nanjing Normal University,Nanjing,Jiangsu 210023,China [2]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China [3]Schoolof Chemistry,Sun Yat-Sen University,Guangzhou,Guangdong 510275,China [4]School of Chemistry and Chemial Enginering,Nanjing University,Nanjing,Jingsu 210023,China [5]School of Pharmaceutical Science and Technology,Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences,Hangzhou,Zhejiang 310024,China

出　　处：《Chinese Journal of Chemistry》2022年第10期1156-1164,共9页中国化学（英文版）

基　　金：We thank NSFC(Nos.22077066,21771109,21778033,21701195,21837006,21977052 and 21907101).

摘　　要：Metallodrugs with fine-tuned coordination between metals and bioactive ligands can achieve cytotoxic effects in cancer therapy and have been considered as a new approach for drug design.However,it has yet to be elucidated whether these metallodrugs target epitranscriptomic proteins for gene expression regulation.This report describes a rhein-based Rh(l)-arene complex,Rh1,that exhibited promising antiproliferative ffects in several tumor cellines.Rh1 induced cell death through the autophagy,cell cycle arrest,and accumulation of intracllular reactive oxygen species(ROs),In addition,Rh1 upregulated the global N^(6)-methyladenosine(m^(6)A)levels in A549 cells in the fat mass-and obesity-associated protein(FTO)-dependent manner.Collectively,the metal-based FTO inhibitor Rh1 effectively suppressed tumor cell proliferation and modulated the abundance of cellular m^(6)A,highlighting the potential of metal-based agents to target and regulate epitranscriptomics for tumor suppression.

关 键 词：RHODIUM mRNA ANTIPROLIFERATION FTO m^(6)A 

分 类 号：O62[理学—有机化学]