Antitumor Activity and Mechanistic Insights of a Mitochondria-Targeting Cu(I) Complex - Details

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Using　copper-ionophores　to　translocate　extracellular　copper　into　mitochondria　is　a　clinically　validated　anticancer　strategy　that　has　been　identified　as　a　new　type　of　regulated　cell　death　termed　“cuproptosis.”　This　study　reports　a　mitochondria-targeting　Cu(I)　complex,　Cu(I)Br(PPh3)3　(CBP),　consisting　of　a　cuprous　ion　coordinated　by　three　triphenylphosphine　moieties　and　a　Br　atom.　CBP　exhibited　antitumor　and　antimetastatic　efficacy　in　vitro　and　in　vivo　by　specifically　targeting　mitochondria　instigating　mitochondrial　dysfunction.　The　cytotoxicity　of　CBP　could　only　be　reversed　by　a　copper　chelator　rather　than　inhibitors　of　the　known　cell　death,　indicating　copper-dependent　cytotoxicity.　Furthermore,　CBP　induced　the　oligomerization　of　lipoylated　proteins　and　the　loss　of　Fe-S　cluster　proteins,　consistent　with　characteristic　features　of　cuproptosis.　Additionally,　CBP　induced　remarkable　intracellular　generation　of　reactive　oxygen　species　(ROS)　through　a　Fenton-like　reaction,　indicating　a　complex　antitumor　mechanism.　This　is　a　proof-of-concept　study　exploiting　the　antitumor　activity　and　mechanism　of　the　Cu(I)-based　mitochondria-targeting　therapy.　©　2024　American　Chemical　Society.

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[ 1 ] [Xu S.]College of Chemistry and Materials Science, Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, Fujian Normal University, 32 Shangsan Road, Fuzhou, 350007, China
[ 2 ] [Hao Y.]College of Biological Science and Engineering, Fuzhou University, Fujian, Fuzhou, 350108, China
[ 3 ] [Xu X.]College of Biological Science and Engineering, Fuzhou University, Fujian, Fuzhou, 350108, China
[ 4 ] [Huang L.]College of Biological Science and Engineering, Fuzhou University, Fujian, Fuzhou, 350108, China
[ 5 ] [Liang Y.]College of Biological Science and Engineering, Fuzhou University, Fujian, Fuzhou, 350108, China
[ 6 ] [Liao J.]College of Biological Science and Engineering, Fuzhou University, Fujian, Fuzhou, 350108, China
[ 7 ] [Yang J.-R.]College of Chemistry and Materials Science, Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, Fujian Normal University, 32 Shangsan Road, Fuzhou, 350007, China
[ 8 ] [Zhou Y.]College of Biological Science and Engineering, Fuzhou University, Fujian, Fuzhou, 350108, China
[ 9 ] [Zhou Y.]College of Chemistry, Fuzhou University, Fujian, Fuzhou, 350108, China
[ 10 ] [Huang M.]College of Biological Science and Engineering, Fuzhou University, Fujian, Fuzhou, 350108, China
[ 11 ] [Huang M.]College of Chemistry, Fuzhou University, Fujian, Fuzhou, 350108, China
[ 12 ] [Du K.-Z.]College of Chemistry and Materials Science, Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, Fujian Normal University, 32 Shangsan Road, Fuzhou, 350007, China
[ 13 ] [Zhang C.]College of Biological Science and Engineering, Fuzhou University, Fujian, Fuzhou, 350108, China
[ 14 ] [Xu P.]College of Biological Science and Engineering, Fuzhou University, Fujian, Fuzhou, 350108, China

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Journal of Medicinal Chemistry

ISSN： 0022-2623

Year： 2024

Issue： 10

Volume： 67

Page： 7911-7920

6 . 9 0 0

JCR@2023

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SCOPUS Cited Count： 9

ESI Highly Cited Papers on the List： 0 Unfold All

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30 Days PV： 1

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