Advances in antitumor and antibacterial activities of N-heterocyclic carbine-metal complexes
LU Qianqian1,2* LIU Ying1,2* YAN Mi1,2 LIU Binbin1,2 CAI Yi1,2 WANG Jun1,3 ZOU Lili1,2
1.Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Hubei Province, Yichang 443000, China;
2.the Institution of Infection and Inflammation, Medical College, China Three Gorges University, Hubei Province, Yichang 443000, China;
3.Department of Science and Technology, the People’s Hospital of China Three Gorges University, Hubei Province, Yichang 443000, China
Abstract：Since Arduengo’s first successful isolation of stable free N-heterocyclic carbinol compounds (NHC) in 1991, its research as a novel ligand for transition metal complexes has developed rapidly. NHC metal complexes deserve special attention for their therapeutic applications in addition to their wide range of applications in catalysis, synthesis and materials. Recent studies have revealed that NHC-metal complexes exhibit good biological activities in anti-tumor and anti-microbial aspects and have great application prospects. Based on this, a brief review of the anti-malignant proliferative activity of NHC-gold (Au), NHC-silver (Ag), NHC-palladium (Pd), and NHC-platinum and the anti-microbial activity of NHC-Au, NHC-Ag, and NHC-Pd is presented.
卢倩倩1,2* 刘英1,2* 严密1,2 刘彬彬1,2 蔡轶1,2 王君1,3 邹黎黎1,2. N-杂环卡宾金属配合物抗肿瘤和抗菌活性的研究进展[J]. 中国医药导报, 2022, 19(32): 31-34,46.
LU Qianqian1,2* LIU Ying1,2* YAN Mi1,2 LIU Binbin1,2 CAI Yi1,2 WANG Jun1,3 ZOU Lili1,2. Advances in antitumor and antibacterial activities of N-heterocyclic carbine-metal complexes. 中国医药导报, 2022, 19(32): 31-34,46.
[1] Wanzlick HW，Kleiner HJ，Nucleophile Carben-Chemie. Neue Verbindungen vom Typ des Bis-[1.3-diphenyl-imidazolidinylidens-（2）] &dagger [J]. Chem Ber，1961，73（14）：1208-1212.
[2] Wanzlick HW. Aspects of Nucleophilic Carbene Chemistry [J]. Angew Chem Int Ed in Engl，1962，1（2）：75-80.
[3] Wanzlick HW，Kleiner HJ. Nucleophile Carben-Chemie Darstellung des Bis-[1.3-diphenyl-imidazolidinyliden-（2）] [J]. Angewandte Chemie，1961，73（14）：493.
[4] Dada O. Synthesis and cytotoxicity studies of novel NHC–Gold（Ⅰ） pseudohalides and thiolates [J]. J Organomet Chem，2017，840：30-37.
[5] Sirindil F，Nolan SP，Dagorne S，et al. Synthesis，Characterization and Catalytic Activity of NHC Gold（Ⅰ） Polyoxometalate Complexes [J]. Chemistry，2018，24（48）：12630-12637.
[6] Lemke J，Pinto A，Niehoff P，et al. Synthesis，structural characterisation and anti-proliferative activity of NHC gold amino acid and peptide conjugates [J]. Dalton Trans，2009（35）：7063-7070.
[7] Atif M，Bhatti HN，Haque RA，et al. Synthesis，Structure，and Anticancer Activity of Symmetrical and Non-symmetrical Silver（Ⅰ）-N-Heterocyclic Carbene Complexes [J]. Appl Biochem Biotechnol，2020，191（3）：1171-1189.
[8] Wong VH，Vummaleti SV，Cavallo L，et al. Synthesis，Structure and Catalytic Activity of NHC-Ag（Ⅰ） Carboxylate Complexes [J]. Chemistry，2016，22（37）：13320-13327.
[9] Liu YF，Wang Z，Shi JW，et al. NHC-Ag（Ⅰ）-Catalyzed Three-Component 1，3-Dipolar Cycloaddition To Provide Polysubstituted Dihydro-/Tetrahydrofurans [J]. J Org Chem，2015，80（24）：12733-12739.
[10] Peng HM，Song G，Li Y，et al. Synthesis，structures，and solution dynamics of palladium complexes of quinoline-functionalized N-heterocyclic carbenes [J]. Inorg Chem，2008， 47（18）：8031-8043.
[11] Yang J，Wang L. Synthesis and characterization of dinuclear NHC-palladium complexes and their applications in the Hiyama reactions of aryltrialkyoxysilanes with aryl chlorid- es [J]. Dalton Trans，2012，41（39）：12031-12037.
[12] Yang L，Guan P，He P，et al. Synthesis and characterization of novel chiral NHC-palladium complexes and their application in copper-free Sonogashira reactions [J]. Dalton Trans，2012，41（16）：5020-5025.
[13] Bouché M，Bonnefont A，Achard T，et al. Exploring diversity in platinum（Ⅳ） N-heterocyclic carbene complexes：synthesis，characterization，reactivity and biological evaluation [J]. Dalton Trans，2018，47（33）：11491-11502.
[14] Rehm T，Rothemund M，Dietel T，et al. Synthesis，structures and cytotoxic effects in vitro of cis- and trans-[Pt（Ⅳ）Cl（4）（NHC）（2）] complexes and their Pt（Ⅱ） precursors [J]. Dalton Trans，2019，48（43）：16358-16365.
[15] Monney A，Venkatachalam G，Albrecht M. Synthesis and catalytic activity of histidine-based NHC ruthenium complexes [J]. Dalton Trans，2011，40（12）：2716-2719.
[16] Merino E，Poli E，Díaz U，et al. Synthesis and characterization of new ruthenium N-heterocyclic carbene Hoveyda Ⅱtype complexes. Study of reactivity in ring closing metathesis reactions [J]. Dalton Trans，2012，41（36）：10913-10918.
[17] Zou T，Lok CN，Wan PK，et al. Anticancer metal-N-heterocyclic carbene complexes of gold，platinum and palladium [J]. Curr Opin Chem Biol，2018，43：30-36.
[18] Bazzicalupi C，Ferraroni M，Papi F，et al. Determinants for Tight and Selective Binding of a Medicinal Dicarbene Gold （Ⅰ） Complex to a Telomeric DNA G-Quadruplex：a Joint ESI MS and XRD Investigation [J]. Angew Chem Int Ed Engl，2016，55（13）：4256-4259.
[19] Fung SK，Zou T，Cao B，et al. Cyclometalated Gold（Ⅲ） Complexes Containing N-Heterocyclic Carbene Ligands Engage Multiple Anti-Cancer Molecular Targets [J]. Angew Chem Int Ed Engl，2017，56（14）：3892-3896.
[20] Hickey JL，Ruhayel RA，Barnard PJ，et al. Mitochondria-targeted chemotherapeutics：the rational design of gold（Ⅰ） N-heterocyclic carbene complexes that are selectively toxic to cancer cells and target protein selenols in preference to thiols [J]. J Am Chem Soc，2008，130（38）：12570- 12571.
[21] Liu W，Bensdorf K，Proetto M，et al. NHC gold halide complexes derived from 4，5-diarylimidazoles：synthesis，structural analysis，and pharmacological investigations as potential antitumor agents [J]. J Med Chem，2011，54（24）：8605- 8615.
[22] Mui YF，Fernández-Gallardo J，Elie BT，et al. Titanocene- Gold Complexes Containing N-Heterocyclic Carbene Ligands Inhibit Growth of Prostate，Renal，and Colon Cancers in Vitro [J]. Organometallics，2016，35（9）：1218-1227.
[23] Schuh E，Pflüger C，Citta A，et al. Gold（Ⅰ） carbene complexes causing thioredoxin 1 and thioredoxin 2 oxidation as potential anticancer agents [J]. J Med Chem，2012，55（11）：5518-5528.
[24] Eloy L，Jarrousse AS，Teyssot ML，et al. Anticancer activity of silver-N-heterocyclic carbene complexes：caspase-independent induction of apoptosis via mitochondrial apoptosis-inducing factor （AIF） [J]. Chem Med Chem，2012，7（5）：805-814.
[25] Li Y，Liu GF，Tan CP，et al. Antitumor properties and mechanisms of mitochondria-targeted Ag（Ⅰ） and Au（Ⅰ） complexes containing N-heterocyclic carbenes derived from cyclophanes [J]. Metallomics，2014，6（8）：1460-1468.
[26] Rosenberg B，VanCamp L，Trosko JE，et al. Platinum compounds：a new class of potent antitumour agents [J]. Nature，1969，222（5191）：385-386.
[27] Harlepp S，Chardon E，Bouché M，et al. N-Heterocyclic Carbene-Platinum Complexes Featuring an Anthracenyl Moiety：Anti-Cancer Activity and DNA Interaction [J]. Int J Mol Sci，2019，20（17）：4198.
[28] Chekkat N，Dahm G，Chardon E，et al. N-Heterocyclic Carbene-Polyethylenimine Platinum Complexes with Potent in Vitro and in Vivo Antitumor Efficacy [J]. Bioconjug Chem，2016，27（8）：1942-1948.
[29] Kapdi AR，Fairlamb IJ. Anti-cancer palladium complexes：a focus on PdX2L2，palladacycles and related complexes [J]. Chem Soc Rev，2014，43（13）：4751-4777.
[30] Fong TT，Lok CN，Chung CY，et al. Cyclometalated Palladium（Ⅱ） N-Heterocyclic Carbene Complexes：Anticancer Agents for Potent in Vitro Cytotoxicity and in Vivo Tumor Growth Suppression [J]. Angew Chem Int Ed Engl，2016，55（39）：11935-11939.
[31] Scattolin T，Bortolamiol E，Palazzolo S，et al. The anticancer activity of an air-stable Pd（Ⅰ）-NHC （NHC = N-heterocyclic carbene） dimer [J]. Chem Commun （Camb），2020， 56（81）：12238-12241.
[32] Johnstone TC，Suntharalingam K，Lippard SJ. The Next Generation of Platinum Drugs：Targeted Pt（Ⅱ） Agents，Nanoparticle Delivery，and Pt（Ⅳ） Prodrugs [J]. Chem Rev，2016，116（5）：3436-3486.
[33] Basu U，Banik B，Wen R，et al. The Platin-X series：activation，targeting，and delivery [J]. Dalton Trans，2016，45（33）：12992-13004.
[34] Vellé A，Maguire R，Kavanagh K，et al. Steroid-Au（Ⅰ）-NHC Complexes：Synthesis and Antibacterial Activity [J]. Chem Med Chem，2017，12（11）：841-844.
[35] Fernández GA，Vela Gurovic MS，Olivera NL，et al. Antibacterial properties of water-soluble gold（Ⅰ） N-heterocyclic carbene complexes [J]. J Inorg Biochem，2014，135：54-57.
[36] Lansdown AB. A review of the use of silver in wound care：facts and fallacies [J]. Br J Nurs，2004，13（6 Suppl）：S6- S19.
[37] Varna D，Zainuddin DI，Hatzidimitriou AG，et al. Homoleptic and heteroleptic silver（Ⅰ） complexes bearing diphosphane and thioamide ligands：Synthesis，structures，DNA interactions and antibacterial activity studies [J]. Mater Sci Eng C Mater Biol Appl，2019，99：450-459.
[38] Aher S，Das A，Muskawar P，et al. In vitro antimicrobial evaluation，effects of halide concentration and hemolysis study of silver-N-heterocyclic carbene complexes [J]. Research on Chemical Intermediates，2018，44（3）：2099- 2110.
[39] Browne N，Hackenberg F，Streciwilk W，et al. Assessment of in vivo antimicrobial activity of the carbene silver（Ⅰ） acetate derivative SBC3 using Galleria mellonella larvae [J]. Biometals，2014，27（4）：745-752.
[40] O’Loughlin J，Napolitano S，Alkhathami F，et al. The Antibacterial Drug Candidate SBC3 is a Potent Inhibitor of Bacterial Thioredoxin Reductase [J]. Chembiochem，2021， 22（6）：1093-1098.
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