Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Review Article

Fluorinated-NHC Transition Metal Complexes: Leading Characters as Potential Anticancer Metallodrugs

Author(s): Ernesto Rufino-Felipe, Raúl Colorado-Peralta, Viviana Reyes-Márquez , Hugo Valdés and David Morales-Morales*

Volume 21, Issue 8, 2021

Published on: 08 September, 2020

Page: [938 - 948] Pages: 11

DOI: 10.2174/1871520620666200908103452

Price: $65

Abstract

In the last 20 years, N-Heterocyclic Carbene (NHC) ligands have been ubiquitous in biological and medicinal chemistry. Part of their success lies in the tremendous number of topologies that can be synthesized and thus finely tuned that have been described so far. This is particularly true in the case of those derivatives, including fluorine or fluorinated fragments on their NHC moieties, gaining much attention due to their enhanced biological properties and turning them into excellent candidates for the development of novel metallodrugs. Thus, this review summarizes the development that fluorinated-NHC transition metal complexes have had and their impact on cancer treatment.

Keywords: Cytotoxicity, fluorinated complexes, NHC complexes, cancer, N-heterocyclic Carbene (NHC), fluorine, metallodrugs.

Graphical Abstract
[1]
Stewart, B.W.; Wild, C.P., Eds.; World Cancer Report; International Agency for Research on Cancer: Lyon, 2014.
[2]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[3]
Dilruba, S.; Kalayda, G.V. Platinum-based drugs: Past, present and future. Cancer Chemother. Pharmacol., 2016, 77(6), 1103-1124.
[http://dx.doi.org/10.1007/s00280-016-2976-z] [PMID: 26886018]
[4]
Chen, X.; Wu, Y.; Dong, H.; Zhang, C-Y.; Zhang, Y. Platinum-based agents for individualized cancer treatment. Curr. Mol. Med., 2013, 13(10), 1603-1612.
[http://dx.doi.org/10.2174/1566524013666131111125515] [PMID: 24206132]
[5]
Kartalou, M.; Essigmann, J.M. Mechanisms of resistance to cisplatin. Mutat. Res., 2001, 478(1-2), 23-43.
[http://dx.doi.org/10.1016/S0027-5107(01)00141-5] [PMID: 11406167]
[6]
Kartalou, M.; Essigmann, J.M. Recognition of cisplatin adducts by cellular proteins. Mutat. Res., 2001, 478(1-2), 1-21.
[http://dx.doi.org/10.1016/S0027-5107(01)00142-7] [PMID: 11406166]
[7]
Fuertes, M.A.; Castilla, J.; Alonso, C.; Pérez, J.M. Cisplatin biochemical mechanism of action: From cytotoxicity to induction of cell death through interconnections between apoptotic and necrotic pathways. Curr. Med. Chem., 2003, 10(3), 257-266.
[http://dx.doi.org/10.2174/0929867033368484] [PMID: 12570712]
[8]
Dasari, S.; Tchounwou, P.B. Cisplatin in cancer therapy: Molecular mechanisms of action. Eur. J. Pharmacol., 2014, 740, 364-378.
[http://dx.doi.org/10.1016/j.ejphar.2014.07.025] [PMID: 25058905]
[9]
Treskes, M.; van der Vijgh, W.J.F. WR2721 as a modulator of cisplatin- and carboplatin-induced side effects in comparison with other chemoprotective agents: A molecular approach. Cancer Chemother. Pharmacol., 1993, 33(2), 93-106.
[http://dx.doi.org/10.1007/BF00685326] [PMID: 8261581]
[10]
Biersack, B.; Schobert, R. Current state of platinum complexes for the treatment of advanced and drug-resistant breast cancers.Advances in Experimental Medicine and Biology; Advances in Experimental Medicine and Biology; Springer International Publishing: Cham, 2019, Vol. 1152, pp. 253-270.
[http://dx.doi.org/10.1007/978-3-030-20301-6_13]
[11]
Stojanovska, V.; McQuade, R.; Rybalka, E.; Nurgali, K. Neurotoxicity associated with platinum-based anti-cancer agents: What are the implications of copper transporters? Curr. Med. Chem., 2017, 24(15), 1520-1536.
[http://dx.doi.org/10.2174/0929867324666170112095428] [PMID: 28079002]
[12]
Breglio, A.M.; Rusheen, A.E.; Shide, E.D.; Fernandez, K.A.; Spielbauer, K.K.; McLachlin, K.M.; Hall, M.D.; Amable, L.; Cunningham, L.L. Cisplatin is retained in the cochlea indefinitely following chemotherapy. Nat. Commun., 2017, 8(1), 1654.
[http://dx.doi.org/10.1038/s41467-017-01837-1] [PMID: 29162831]
[13]
Johnstone, T.C.; Suntharalingam, K.; Lippard, S.J. The next generation of platinum drugs: Targeted Pt(II) agents, nanoparticle delivery, and Pt(IV) prodrugs. Chem. Rev., 2016, 116(5), 3436-3486.
[http://dx.doi.org/10.1021/acs.chemrev.5b00597] [PMID: 26865551]
[14]
Meier-Menches, S.M.; Gerner, C.; Berger, W.; Hartinger, C.G.; Keppler, B.K. Structure-activity relationships for ruthenium and osmium anticancer agents - towards clinical development. Chem. Soc. Rev., 2018, 47(3), 909-928.
[http://dx.doi.org/10.1039/C7CS00332C] [PMID: 29170783]
[15]
Zeng, L.; Gupta, P.; Chen, Y.; Wang, E.; Ji, L.; Chao, H.; Chen, Z-S. The development of anticancer Ruthenium(II) complexes: From single molecule compounds to nanomaterials. Chem. Soc. Rev., 2017, 46(19), 5771-5804.
[http://dx.doi.org/10.1039/C7CS00195A] [PMID: 28654103]
[16]
Hartinger, C.G.; Dyson, P.J. Bioorganometallic chemistry-from teaching paradigms to medicinal applications. Chem. Soc. Rev., 2009, 38(2), 391-401.
[http://dx.doi.org/10.1039/B707077M] [PMID: 19169456]
[17]
Hartinger, C.G.; Phillips, A.D.; Nazarov, A.A. Polynuclear ruthenium, osmium and gold complexes. The quest for innovative anticancer chemotherapeutics. Curr. Top. Med. Chem., 2011, 11(21), 2688-2702.
[http://dx.doi.org/10.2174/156802611798040769] [PMID: 22039871]
[18]
Santini, C.; Pellei, M.; Gandin, V.; Porchia, M.; Tisato, F.; Marzano, C. Advances in copper complexes as anticancer agents. Chem. Rev., 2014, 114(1), 815-862.
[http://dx.doi.org/10.1021/cr400135x] [PMID: 24102434]
[19]
Englinger, B.; Pirker, C.; Heffeter, P.; Terenzi, A.; Kowol, C.R.; Keppler, B.K.; Berger, W. Metal drugs and the anticancer immune response. Chem. Rev., 2019, 119(2), 1519-1624.
[http://dx.doi.org/10.1021/acs.chemrev.8b00396] [PMID: 30489072]
[20]
Mjos, K.D.; Orvig, C. Metallodrugs in medicinal inorganic chemistry. Chem. Rev., 2014, 114(8), 4540-4563.
[http://dx.doi.org/10.1021/cr400460s] [PMID: 24456146]
[21]
John, A.; Ghosh, P. Fascinating frontiers of N/O-functionalized N-heterocyclic carbene chemistry: From chemical catalysis to biomedical applications. Dalton Trans., 2010, 39(31), 7183-7206.
[http://dx.doi.org/10.1039/c002475a] [PMID: 20495733]
[22]
Gasser, G.; Ott, I.; Metzler-Nolte, N. Organometallic anticancer compounds. J. Med. Chem., 2011, 54(1), 3-25.
[http://dx.doi.org/10.1021/jm100020w] [PMID: 21077686]
[23]
Gasser, G.; Metzler-Nolte, N. The potential of organometallic complexes in medicinal chemistry. Curr. Opin. Chem. Biol., 2012, 16(1-2), 84-91.
[http://dx.doi.org/10.1016/j.cbpa.2012.01.013] [PMID: 22366385]
[24]
Zou, T.; Lum, C.T.; Lok, C-N.; Zhang, J-J.; Che, C.M. Chemical biology of anticancer gold(III) and gold(I) complexes. Chem. Soc. Rev., 2015, 44(24), 8786-8801.
[http://dx.doi.org/10.1039/C5CS00132C] [PMID: 25868756]
[25]
Thota, S.; Rodrigues, D.A.; Crans, D.C.; Barreiro, E.J. Ru(II) compounds: Next-generation anticancer metallotherapeutics? J. Med. Chem., 2018, 61(14), 5805-5821.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01689] [PMID: 29446940]
[26]
Liu, W.; Gust, R. Update on metal N-heterocyclic carbene complexes as potential anti-tumor metallodrugs. Coord. Chem. Rev., 2016, 329, 191-213.
[http://dx.doi.org/10.1016/j.ccr.2016.09.004]
[27]
Liu, W.; Gust, R. Metal N-heterocyclic carbene complexes as potential antitumor metallodrugs. Chem. Soc. Rev., 2013, 42(2), 755-773.
[http://dx.doi.org/10.1039/C2CS35314H] [PMID: 23147001]
[28]
Hackenberg, F.; Tacke, M. Benzyl-substituted metallocarbene antibiotics and anticancer drugs. Dalton Trans., 2014, 43(22), 8144-8153.
[http://dx.doi.org/10.1039/C4DT00624K] [PMID: 24770329]
[29]
Oehninger, L.; Rubbiani, R.; Ott, I. N-Heterocyclic carbene metal complexes in medicinal chemistry. Dalton Trans., 2013, 42(10), 3269-3284.
[http://dx.doi.org/10.1039/C2DT32617E] [PMID: 23223752]
[30]
Zou, T.; Lok, C-N.; Wan, P-K.; Zhang, Z-F.; Fung, S.K.; Che, C.M. Anticancer metal-N-heterocyclic carbene complexes of gold, platinum and palladium. Curr. Opin. Chem. Biol., 2018, 43, 30-36.
[http://dx.doi.org/10.1016/j.cbpa.2017.10.014] [PMID: 29136524]
[31]
Zhu, Y.; Han, J.; Wang, J.; Shibata, N.; Sodeoka, M.; Soloshonok, V.A.; Coelho, J.A.S.; Toste, F.D. Modern approaches for asymmetric construction of carbon-fluorine quaternary stereogenic centers: Synthetic challenges and pharmaceutical needs. Chem. Rev., 2018, 118(7), 3887-3964.
[http://dx.doi.org/10.1021/acs.chemrev.7b00778] [PMID: 29608052]
[32]
Moschner, J.; Stulberg, V.; Fernandes, R.; Huhmann, S.; Leppkes, J.; Koksch, B. Approaches to obtaining fluorinated α-amino acids. Chem. Rev., 2019, 119(18), 10718-10801.
[http://dx.doi.org/10.1021/acs.chemrev.9b00024] [PMID: 31436087]
[33]
Wang, J.; Sánchez-Roselló, M.; Aceña, J.L.; del Pozo, C.; Sorochinsky, A.E.; Fustero, S.; Soloshonok, V.A.; Liu, H. Fluorine in pharmaceutical industry: Fluorine-containing drugs introduced to the market in the last decade (2001-2011). Chem. Rev., 2014, 114(4), 2432-2506.
[http://dx.doi.org/10.1021/cr4002879] [PMID: 24299176]
[34]
Zhou, Y.; Wang, J.; Gu, Z.; Wang, S.; Zhu, W.; Aceña, J.L.; Soloshonok, V.A.; Izawa, K.; Liu, H. Next generation of fluorine-containing pharmaceuticals, compounds currently in Phase II-III clinical trials of major pharmaceutical companies: New structural trends and therapeutic areas. Chem. Rev., 2016, 116(2), 422-518.
[http://dx.doi.org/10.1021/acs.chemrev.5b00392] [PMID: 26756377]
[35]
Isanbor, C.; O’Hagan, D. Fluorine in medicinal chemistry: A review of anti-cancer agents. J. Fluor. Chem., 2006, 127, 303-319.
[http://dx.doi.org/10.1016/j.jfluchem.2006.01.011]
[36]
Kirk, K.L. Fluorine in medicinal chemistry: Recent therapeutic applications of fluorinated small molecules. J. Fluor. Chem., 2006, 127, 1013-1029.
[http://dx.doi.org/10.1016/j.jfluchem.2006.06.007]
[37]
Li, F.; Collins, J.G.; Keene, F.R. Ruthenium complexes as antimicrobial agents. Chem. Soc. Rev., 2015, 44(8), 2529-2542.
[http://dx.doi.org/10.1039/C4CS00343H] [PMID: 25724019]
[38]
Alessio, E.; Messori, L. NAMI-A and KP1019/1339, two iconic ruthenium anticancer drug candidates face-to-face: A case story in medicinal inorganic chemistry. Molecules, 2019, 24(10), 1995.
[http://dx.doi.org/10.3390/molecules24101995] [PMID: 31137659]
[39]
Golbaghi, G.; Castonguay, A. Rationally designed ruthenium complexes for breast cancer therapy. Molecules, 2020, 25(2), 265.
[http://dx.doi.org/10.3390/molecules25020265] [PMID: 31936496]
[40]
Riccardi, C.; Musumeci, D.; Trifuoggi, M.; Irace, C.; Paduano, L.; Montesarchio, D. Anticancer Ruthenium(III) complexes and Ru(III)-containing nanoformulations: An update on the mechanism of action and biological activity. Pharmaceuticals (Basel), 2019, 12(4), 146.
[http://dx.doi.org/10.3390/ph12040146] [PMID: 31561546]
[41]
Kostova, I. Ruthenium complexes as anticancer agents. Curr. Med. Chem., 2006, 13(9), 1085-1107.
[http://dx.doi.org/10.2174/092986706776360941] [PMID: 16611086]
[42]
Kenny, R.G.; Marmion, C.J. Toward multi-targeted platinum and ruthenium drugs-A new paradigm in cancer drug treatment regimens? Chem. Rev., 2019, 119(2), 1058-1137.
[http://dx.doi.org/10.1021/acs.chemrev.8b00271] [PMID: 30640441]
[43]
Scolaro, C.; Bergamo, A.; Brescacin, L.; Delfino, R.; Cocchietto, M.; Laurenczy, G.; Geldbach, T.J.; Sava, G.; Dyson, P.J. In vitro and in vivo evaluation of ruthenium(II)-arene PTA complexes. J. Med. Chem., 2005, 48(12), 4161-4171.
[http://dx.doi.org/10.1021/jm050015d] [PMID: 15943488]
[44]
Scolaro, C.; Hartinger, C.G.; Allardyce, C.S.; Keppler, B.K.; Dyson, P.J. Hydrolysis study of the bifunctional antitumour compound RAPTA-C.[Ru(eta6-p-cymene)Cl2(pta)] J. Inorg. Biochem., 2008, 102(9), 1743-1748.
[http://dx.doi.org/10.1016/j.jinorgbio.2008.05.004] [PMID: 18582946]
[45]
Chatterjee, S.; Kundu, S.; Bhattacharyya, A.; Hartinger, C.G.; Dyson, P.J. The ruthenium(II)-arene compound RAPTA-C induces apoptosis in EAC cells through mitochondrial and p53-JNK pathways. J. Biol. Inorg. Chem., 2008, 13(7), 1149-1155.
[http://dx.doi.org/10.1007/s00775-008-0400-9] [PMID: 18597125]
[46]
Nazarov, A.A.; Meier, S.M.; Zava, O.; Nosova, Y.N.; Milaeva, E.R.; Hartinger, C.G.; Dyson, P.J. Protein ruthenation and DNA alkylation: Chlorambucil-functionalized RAPTA complexes and their anticancer activity. Dalton Trans., 2015, 44(8), 3614-3623.
[http://dx.doi.org/10.1039/C4DT02764G] [PMID: 25407500]
[47]
Blunden, B.M.; Lu, H.; Stenzel, M.H. Enhanced delivery of the RAPTA-C macromolecular chemotherapeutic by conjugation to degradable polymeric micelles. Biomacromolecules, 2013, 14(12), 4177-4188.
[http://dx.doi.org/10.1021/bm4013919] [PMID: 24266669]
[48]
Adeniyi, A.A.; Ajibade, P.A. Effects of bidentate coordination on the molecular properties rapta-C based complex using theoretical approach. J. Mol. Model., 2013, 19(3), 1325-1338.
[http://dx.doi.org/10.1007/s00894-012-1683-x] [PMID: 23187687]
[49]
Kilpin, K.J.; Cammack, S.M.; Clavel, C.M.; Dyson, P.J. Ruthenium(II) arene PTA (RAPTA) complexes: Impact of enantiomerically pure chiral ligands. Dalton Trans., 2013, 42(6), 2008-2014.
[http://dx.doi.org/10.1039/C2DT32333H] [PMID: 23187957]
[50]
Castonguay, A.; Doucet, C.; Juhas, M.; Maysinger, D. New ruthenium(II)-letrozole complexes as anticancer therapeutics. J. Med. Chem., 2012, 55(20), 8799-8806.
[http://dx.doi.org/10.1021/jm301103y] [PMID: 22991922]
[51]
Chakree, K.; Ovatlarnporn, C.; Dyson, P.J.; Ratanaphan, A. Altered DNA binding and amplification of human breast cancer suppressor gene BRCA1 induced by a novel antitumor compound., [Ru(η(6)-pphenylethacrynate) Cl2(pta)] Int. J. Mol. Sci., 2012, 13(10), 13183-13202.
[http://dx.doi.org/10.3390/ijms131013183] [PMID: 23202946]
[52]
Nowak-Sliwinska, P.; van Beijnum, J.R.; Casini, A.; Nazarov, A.A.; Wagnieres, G.; van den Bergh, H.; Dyson, P.J.; Griffioen, A.W. Organometallic ruthenium(II) arene compounds with antiangiogenic activity. J. Med. Chem., 2011, 54(11), 3895-3902.
[http://dx.doi.org/10.1021/jm2002074] [PMID: 21534534]
[53]
Casini, A.; Karotki, A.; Gabbiani, C.; Rugi, F.; Vašák, M.; Messori, L.; Dyson, P.J. Reactivity of an antimetastatic organometallic ruthenium compound with metallothionein-2: Relevance to the mechanism of action. Metallomics, 2009, 1(5), 434-441.
[http://dx.doi.org/10.1039/b909185h] [PMID: 21305148]
[54]
Casini, A.; Gabbiani, C.; Michelucci, E.; Pieraccini, G.; Moneti, G.; Dyson, P.J.; Messori, L. Exploring metallodrug-protein interactions by mass spectrometry: Comparisons between platinum coordination complexes and an organometallic ruthenium compound. J. Biol. Inorg. Chem., 2009, 14(5), 761-770.
[http://dx.doi.org/10.1007/s00775-009-0489-5] [PMID: 19288144]
[55]
Hartinger, C.G.; Casini, A.; Duhot, C.; Tsybin, Y.O.; Messori, L.; Dyson, P.J. Stability of an organometallic ruthenium-ubiquitin adduct in the presence of glutathione: Relevance to antitumour activity. J. Inorg. Biochem., 2008, 102(12), 2136-2141.
[http://dx.doi.org/10.1016/j.jinorgbio.2008.08.002] [PMID: 18834634]
[56]
Sojka, M.; Fojtu, M.; Fialova, J.; Masarik, M.; Necas, M.; Marek, R. Locked and loaded: Ruthenium(II)-capped cucurbit[n]uril-based rotaxanes with antimetastatic properties. Inorg. Chem., 2019, 58(16), 10861-10870.
[http://dx.doi.org/10.1021/acs.inorgchem.9b01203] [PMID: 31355636]
[57]
Briš, A.; Jašík, J.; Turel, I.; Roithová, J. Anti-cancer organoruthenium(ii) complexes and their interactions with cysteine and its analogues. A mass-spectrometric study. Dalton Trans., 2019, 48(8), 2626-2634.
[http://dx.doi.org/10.1039/C8DT04350G] [PMID: 30702097]
[58]
Lv, G.; Guo, L.; Qiu, L.; Yang, H.; Wang, T.; Liu, H.; Lin, J. Lipophilicity-dependent ruthenium N-heterocyclic carbene complexes as potential anticancer agents. Dalton Trans., 2015, 44(16), 7324-7331.
[http://dx.doi.org/10.1039/C5DT00169B] [PMID: 25797411]
[59]
Giraldi, T.; Sava, G.; Mestroni, G.; Zassinovich, G.; Stolfa, D. Antitumor action of rhodium (I) and iridium (I) complexes. Chem. Biol. Interact., 1978, 22(2-3), 231-238.
[http://dx.doi.org/10.1016/0009-2797(78)90128-X] [PMID: 699174]
[60]
Ott, I. Metal N-heterocyclic carbene complexes in medicinal chemistry. Adv. Inorg. Chem., 2020, 75, 121-148.
[http://dx.doi.org/10.1016/bs.adioch.2019.10.008]
[61]
Liu, Z.; Sadler, P.J. Organoiridium complexes: Anticancer agents and catalysts. Acc. Chem. Res., 2014, 47(4), 1174-1185.
[http://dx.doi.org/10.1021/ar400266c] [PMID: 24555658]
[62]
Valdés, H.; Canseco-González, D.; Germán-Acacio, J.M.; Morales-Morales, D. Xanthine based N-Heterocyclic Carbene (NHC). Complexes. J. Organomet. Chem., 2018, 867, 51-54.
[http://dx.doi.org/10.1016/j.jorganchem.2018.01.008]
[63]
Sava, G.; Zorzet, S.; Paressin, L. Coordination metal complexes of Rh(I), Ir(I) and Ru(II): Recent advances on antimetastatic activity on solid mouse tumors. Inorg. Chim. Acta, 1987, 137, 69-71.
[http://dx.doi.org/10.1016/S0020-1693(00)87119-4]
[64]
Daubit, I.M.; Wolf, J.; Metzler-Nolte, N. Rhodium(I) and Iridium(I) N-Heterocyclic carbene complexes of imidazolium functionalized amino acids and peptides. J. Organomet. Chem., 2020, 909121096
[http://dx.doi.org/10.1016/j.jorganchem.2019.121096]
[65]
Gothe, Y.; Marzo, T.; Messori, L.; Metzler-Nolte, N. Cytotoxic activity and protein binding through an unusual oxidative mechanism by an iridium(I)-NHC complex. Chem. Commun. (Camb.), 2015, 51(15), 3151-3153.
[http://dx.doi.org/10.1039/C4CC10014J] [PMID: 25605442]
[66]
Gothe, Y.; Marzo, T.; Messori, L.; Metzler-Nolte, N. Iridium(I) compounds as prospective anticancer agents: Solution chemistry, antiproliferative profiles and protein interactions for a series of Iridium(I) N-heterocyclic carbene complexes. Chemistry, 2016, 22(35), 12487-12494.
[http://dx.doi.org/10.1002/chem.201601542] [PMID: 27443984]
[67]
Gothe, Y.; Romero-Canelón, I.; Marzo, T.; Sadler, P.J.; Messori, L.; Metzler-Nolte, N. Synthesis and mode of action studies on Iridium(I)-NHC anticancer drug candidates. Eur. J. Inorg. Chem., 2018, 20-21, 2461-2470.
[http://dx.doi.org/10.1002/ejic.201800225]
[68]
McConnell, J.R.; Rananaware, D.P.; Ramsey, D.M.; Buys, K.N.; Cole, M.L.; McAlpine, S.R. A potential rhodium cancer therapy: studies of a cytotoxic organorhodium(I) complex that binds DNA. Bioorg. Med. Chem. Lett., 2013, 23(9), 2527-2531.
[http://dx.doi.org/10.1016/j.bmcl.2013.03.016] [PMID: 23541673]
[69]
Oehninger, L.; Küster, L.N.; Schmidt, C.; Muñoz-Castro, A.; Prokop, A.; Ott, I. A chemical-biological evaluation of rhodium(I) N-heterocyclic carbene complexes as prospective anticancer drugs. Chemistry, 2013, 19(52), 17871-17880.
[http://dx.doi.org/10.1002/chem.201302819] [PMID: 24243420]
[70]
Oehninger, L.; Spreckelmeyer, S.; Holenya, P.; Meier, S.M.; Can, S.; Alborzinia, H.; Schur, J.; Keppler, B.K.; Wölfl, S.; Ott, I. Rhodium(I) N-heterocyclic carbene bioorganometallics as in vitro antiproliferative agents with distinct effects on cellular signaling. J. Med. Chem., 2015, 58(24), 9591-9600.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01159] [PMID: 26595649]
[71]
Simpson, P.V.; Schmidt, C.; Ott, I.; Bruhn, H.; Schatzschneider, U. Synthesis, cellular uptake and biological activity against pathogenic microorganisms and cancer cells of rhodium and iridium N-heterocyclic carbene complexes bearing charged substituents. Eur. J. Inorg. Chem., 2013, 32, 5547-5554.
[http://dx.doi.org/10.1002/ejic.201300820]
[72]
Lo, K.K-W.; Zhang, K.Y. Iridium(III) complexes as therapeutic and bioimaging reagents for cellular applications. RSC Adv., 2012, 2, 12069-12083.
[http://dx.doi.org/10.1039/c2ra20967e]
[73]
Geldmacher, Y.; Oleszak, M.; Sheldrick, W.S. Rhodium(III) and Iridium(III) complexes as anticancer agents. Inorg. Chim. Acta, 2012, 393, 84-102.
[http://dx.doi.org/10.1016/j.ica.2012.06.046]
[74]
Xu, Z.; Zhang, Y.; Zhang, S.; Jia, X.; Zhong, G.; Yang, Y.; Du, Q.; Li, J.; Liu, Z. Novel half-sandwich iridium O^C (carbene)-Complexes: In vitro and in vivo tumor growth suppression and pro-apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes. Cancer Lett., 2019, 447, 75-85.
[http://dx.doi.org/10.1016/j.canlet.2019.01.018] [PMID: 30673591]
[75]
Maftei, E.; Maftei, C.V.; Jones, P.G.; Freytag, M.; Franz, M.H.; Kelter, G.; Fiebig, H-H.; Tamm, M.; Neda, I. Trifluoromethylpyridine-substituted N-heterocyclic carbenes related to natural products: Synthesis, structure, and potential antitumor activity of some corresponding Gold(I), Rhodium(I), and Iridium(I). Complexes. Helv. Chim. Acta, 2016, 99, 469-481.
[http://dx.doi.org/10.1002/hlca.201500529]
[76]
Sánchez-Mora, A.; Valdés, H.; Ramírez Apan, M.T.; Nieto-Camacho, A.; Hernández Ortega, S.; Canseco-González, D.; Morales-Morales, D. NHC-Ir(I) complexes derived from 5,6-dinitrobenzimidazole. Synthesis, characterization and preliminary evaluation of their in vitro anticancer activity. Inorg. Chim. Acta, 2019, 496119061
[http://dx.doi.org/10.1016/j.ica.2019.119061]
[77]
Kapdi, A.R.; Fairlamb, I.J.S. Anti-cancer palladium complexes: A focus on PdX2L2, palladacycles and related complexes. Chem. Soc. Rev., 2014, 43(13), 4751-4777.
[http://dx.doi.org/10.1039/C4CS00063C] [PMID: 24723061]
[78]
Teyssot, M-L.; Jarrousse, A-S.; Manin, M.; Chevry, A.; Roche, S.; Norre, F.; Beaudoin, C.; Morel, L.; Boyer, D.; Mahiou, R.; Gautier, A. Metal-NHC complexes: A survey of anti-cancer properties. Dalton Trans., 2009, 205(35), 6894-6902.
[http://dx.doi.org/10.1039/b906308k] [PMID: 20449127]
[79]
Lee, J-Y.; Lee, J-Y.; Chang, Y-Y.; Hu, C-H.; Wang, N.M.; Lee, H.M. Palladium complexes with tridentate N-Heterocyclic carbene ligands: Selective “Normal” and ‘Abnormal’ bindings and their anticancer activities. Organometallics, 2015, 34, 4359-4368.
[http://dx.doi.org/10.1021/acs.organomet.5b00586]
[80]
Rehm, T.; Rothemund, M.; Muenzner, J.K.; Noor, A.; Kempe, R.; Schobert, R. Novel cis-[(NHC)1(NHC)2(L)Cl]platinum(ii) complexes - synthesis, structures, and anticancer activities. Dalton Trans., 2016, 45(39), 15390-15398.
[http://dx.doi.org/10.1039/C6DT02350A] [PMID: 27603959]
[81]
Skander, M.; Retailleau, P.; Bourrié, B.; Schio, L.; Mailliet, P.; Marinetti, A. N-heterocyclic carbene-amine Pt(II) complexes, a new chemical space for the development of platinum-based anticancer drugs. J. Med. Chem., 2010, 53(5), 2146-2154.
[http://dx.doi.org/10.1021/jm901693m] [PMID: 20148592]
[82]
Chtchigrovsky, M.; Eloy, L.; Jullien, H.; Saker, L.; Ségal-Bendirdjian, E.; Poupon, J.; Bombard, S.; Cresteil, T.; Retailleau, P.; Marinetti, A. Antitumor trans-N-heterocyclic carbene-amine-Pt(II) complexes: Synthesis of dinuclear species and exploratory investigations of DNA binding and cytotoxicity mechanisms. J. Med. Chem., 2013, 56(5), 2074-2086.
[http://dx.doi.org/10.1021/jm301780s] [PMID: 23421599]
[83]
Karaca, Ö.; Meier-Menches, S.M.; Casini, A.; Kühn, F.E. On the binding modes of metal NHC complexes with DNA secondary structures: Implications for therapy and imaging. Chem. Commun. (Camb.), 2017, 53(59), 8249-8260.
[http://dx.doi.org/10.1039/C7CC03074F] [PMID: 28653066]
[84]
Hashmi, A.S.K. Gold-catalyzed organic reactions. Chem. Rev., 2007, 107(7), 3180-3211.
[http://dx.doi.org/10.1021/cr000436x] [PMID: 17580975]
[85]
Li, Z.; Brouwer, C.; He, C. Gold-catalyzed organic transformations. Chem. Rev., 2008, 108(8), 3239-3265.
[http://dx.doi.org/10.1021/cr068434l] [PMID: 18613729]
[86]
Jiménez-Núñez, E.; Echavarren, A.M. Gold-catalyzed cycloisomerizations of enynes: A mechanistic perspective. Chem. Rev., 2008, 108(8), 3326-3350.
[http://dx.doi.org/10.1021/cr0684319] [PMID: 18636778]
[87]
Arcadi, A. Alternative synthetic methods through new developments in catalysis by gold. Chem. Rev., 2008, 108(8), 3266-3325.
[http://dx.doi.org/10.1021/cr068435d] [PMID: 18651778]
[88]
Krause, N.; Winter, C. Gold-catalyzed nucleophilic cyclization of functionalized allenes: A powerful access to carbo- and heterocycles. Chem. Rev., 2011, 111(3), 1994-2009.
[http://dx.doi.org/10.1021/cr1004088] [PMID: 21314182]
[89]
Dorel, R.; Echavarren, A.M. Gold(I)-catalyzed activation of alkynes for the construction of molecular complexity. Chem. Rev., 2015, 115(17), 9028-9072.
[http://dx.doi.org/10.1021/cr500691k] [PMID: 25844920]
[90]
Miró, J.; Del Pozo, C. Fluorine and gold: A fruitful partnership. Chem. Rev., 2016, 116(19), 11924-11966.
[http://dx.doi.org/10.1021/acs.chemrev.6b00203] [PMID: 27548659]
[91]
Pflästerer, D.; Hashmi, A.S.K. Gold catalysis in total synthesis - recent achievements. Chem. Soc. Rev., 2016, 45(5), 1331-1367.
[http://dx.doi.org/10.1039/C5CS00721F] [PMID: 26673389]
[92]
Asiri, A.M.; Hashmi, A.S.K. Gold-catalysed reactions of diynes. Chem. Soc. Rev., 2016, 45(16), 4471-4503.
[http://dx.doi.org/10.1039/C6CS00023A] [PMID: 27385433]
[93]
Rudolph, M.; Hashmi, A.S.K. Gold catalysis in total synthesis--an update. Chem. Soc. Rev., 2012, 41(6), 2448-2462.
[http://dx.doi.org/10.1039/C1CS15279C] [PMID: 22182942]
[94]
Marion, N.; Nolan, S.P. N-heterocyclic carbenes in gold catalysis. Chem. Soc. Rev., 2008, 37(9), 1776-1782.
[http://dx.doi.org/10.1039/b711132k] [PMID: 18762827]
[95]
Mohr, F., Ed.; Gold Chemistry, 1st ed; Wiley: USA, 2009.
[http://dx.doi.org/10.1002/9783527626724]
[96]
Hashmi, A.S.K.; Toste, F.D., Eds.; Modern Gold Catalyzed Synthesis; ; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2012
[97]
Teyssot, M-L.; Jarrousse, A-S.; Chevry, A.; De Haze, A.; Beaudoin, C.; Manin, M.; Nolan, S.P.; Díez-González, S.; Morel, L.; Gautier, A. Toxicity of copper(I)-NHC complexes against human tumor cells: induction of cell cycle arrest, apoptosis, and DNA cleavage. Chemistry, 2009, 15(2), 314-318.
[http://dx.doi.org/10.1002/chem.200801992] [PMID: 19025730]
[98]
Streciwilk, W.; Hackenberg, F.; Müller Bunz, H.; Tacke, M. Synthesis and cytotoxicity studies of P-benzyl substituted NHC-Copper(I) bromide derivatives. Polyhedron, 2014, 80, 3-9.
[http://dx.doi.org/10.1016/j.poly.2013.11.039]
[99]
Walther, W.; Fichtner, I.; Hackenberg, F.; Streciwilk, W.; Tacke, M. In vitro and in vivo investigations into the carbene copper bromide anticancer drug candidate WBC4. Lett. Drug Des. Discov., 2014, 11, 825-832.
[http://dx.doi.org/10.2174/1570180811666140529004102]
[100]
Tacke, M. benzyl-substituted carbine-metal complexes: Potential for novel antibiotics and anticancer drugs? J. Organomet. Chem., 2015, 782, 17-21.
[http://dx.doi.org/10.1016/j.jorganchem.2014.09.036]
[101]
Elie, M.; Mahoro, G.U.; Duverger, E.; Renaud, J-L.; Daniellou, R.; Gaillard, S. Cytotoxicity of cationic NHC Copper(I) complexes coordinated to 2,2′-bis-pyridyl ligands. J. Organomet. Chem., 2019, 893, 21-31.
[http://dx.doi.org/10.1016/j.jorganchem.2019.04.003]
[102]
Liu, W.; Bensdorf, K.; Hagenbach, A.; Abram, U.; Niu, B.; Mariappan, A.; Gust, R. Synthesis and biological studies of silver N-heterocyclic carbene complexes derived from 4,5-diarylimidazole. Eur. J. Med. Chem., 2011, 46(12), 5927-5934.
[http://dx.doi.org/10.1016/j.ejmech.2011.10.002] [PMID: 22019187]
[103]
Liu, W.; Bensdorf, K.; Proetto, M.; Abram, U.; Hagenbach, A.; Gust, R. NHC gold halide complexes derived from 4,5-diarylimidazoles: Synthesis, structural analysis, and pharmacological investigations as potential antitumor agents. J. Med. Chem., 2011, 54(24), 8605-8615.
[http://dx.doi.org/10.1021/jm201156x] [PMID: 22091836]
[104]
Liu, W.; Bensdorf, K.; Proetto, M.; Hagenbach, A.; Abram, U.; Gust, R. Synthesis, characterization, and in vitro studies of bis[1,3-diethyl-4,5-diarylimidazol-2-ylidene]gold(I/III) complexes. J. Med. Chem., 2012, 55(8), 3713-3724.
[http://dx.doi.org/10.1021/jm3000196] [PMID: 22424185]
[105]
Kaps, L.; Biersack, B.; Müller-Bunz, H.; Mahal, K.; Münzner, J.; Tacke, M.; Mueller, T.; Schobert, R. Gold(I)-NHC complexes of antitumoral diarylimidazoles: Structures, cellular uptake routes and anticancer activities. J. Inorg. Biochem., 2012, 106(1), 52-58.
[http://dx.doi.org/10.1016/j.jinorgbio.2011.08.026] [PMID: 22112840]
[106]
Schmidt, C.; Karge, B.; Misgeld, R.; Prokop, A.; Franke, R.; Brönstrup, M.; Ott, I. Gold(I) NHC complexes: Antiproliferative activity, cellular uptake, inhibition of mammalian and bacterial thioredoxin reductases, and gram-positive directed antibacterial effects. Chemistry, 2017, 23(8), 1869-1880.
[http://dx.doi.org/10.1002/chem.201604512] [PMID: 27865002]
[107]
Rayan, A.; Raiyn, J.; Falah, M. Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity. PLoS One, 2017, 12(11)e0187925
[http://dx.doi.org/10.1371/journal.pone.0187925] [PMID: 29121120]
[108]
Xiao, Z.; Morris-Natschke, S.L.; Lee, K-H. Strategies for the optimization of natural leads to anticancer drugs or drug candidates. Med. Res. Rev., 2016, 36(1), 32-91.
[http://dx.doi.org/10.1002/med.21377] [PMID: 26359649]
[109]
Scattolin, T.; Caligiuri, I.; Canovese, L.; Demitri, N.; Gambari, R.; Lampronti, I.; Rizzolio, F.; Santo, C.; Visentin, F. Synthesis of new allyl palladium complexes bearing purine-based NHC ligands with antiproliferative and proapoptotic activities on human ovarian cancer cell lines. Dalton Trans., 2018, 47(38), 13616-13630.
[http://dx.doi.org/10.1039/C8DT01831F] [PMID: 30207339]
[110]
Eslava-Gonzalez, I.; Valdés, H.; Teresa Ramírez-Apan, M.; Hernández Ortega, S.; Rosario Zermeño-Ortega, M.; Avila Sorrosa, A.; Morales-Morales, D. Synthesis of theophylline-based Iridium(I) N-heterocyclic carbene complexes including fluorinated-thiophenolate ligands. Preliminary evaluation of their in vitro anticancer activity. Inorg. Chim. Acta, 2020, 507119588
[http://dx.doi.org/10.1016/j.ica.2020.119588]
[111]
Bertrand, B.; Stefan, L.; Pirrotta, M.; Monchaud, D.; Bodio, E.; Richard, P.; Le Gendre, P.; Warmerdam, E.; de Jager, M.H.; Groothuis, G.M.M.; Picquet, M.; Casini, A. Caffeine-based Gold(I) N-heterocyclic carbenes as possible anticancer agents: Synthesis and biological properties. Inorg. Chem., 2014, 53(4), 2296-2303.
[http://dx.doi.org/10.1021/ic403011h] [PMID: 24499428]
[112]
Bertrand, B.; Bodio, E.; Richard, P.; Picquet, M.; Le Gendre, P.; Casini, A. Gold(I) N-heterocyclic carbene complexes with an “Activable” ester moiety: Possible biological applications. J. Organomet. Chem., 2015, 775, 124-129.
[http://dx.doi.org/10.1016/j.jorganchem.2014.03.020]
[113]
Bertrand, B.; Citta, A.; Franken, I.L.; Picquet, M.; Folda, A.; Scalcon, V.; Rigobello, M.P.; Le Gendre, P.; Casini, A.; Bodio, E. Gold(I) NHC-based homo- and heterobimetallic complexes: Synthesis, characterization and evaluation as potential anticancer agents. J. Biol. Inorg. Chem., 2015, 20(6), 1005-1020.
[http://dx.doi.org/10.1007/s00775-015-1283-1] [PMID: 26202908]
[114]
Niu, W.; Chen, X.; Tan, W.; Veige, A.S. N-heterocyclic carbene-Gold(I) complexes conjugated to a leukemia-specific DNA aptamer for targeted drug delivery. Angew. Chem. Int. Ed. Engl., 2016, 55(31), 8889-8893.
[http://dx.doi.org/10.1002/anie.201602702] [PMID: 27311814]
[115]
Bertrand, B.; O Connell, M.A.; Waller, Z.A.E.; Bochmann, M.A Gold(III) pincer ligand scaffold for the synthesis of binuclear and bioconjugated complexes: Synthesis and anticancer potential. Chemistry, 2018, 24(14), 3613-3622.
[http://dx.doi.org/10.1002/chem.201705902] [PMID: 29334159]
[116]
Niu, W.; Teng, I-T.; Chen, X.; Tan, W.; Veige, A.S. Aptamer-mediated selective delivery of a cytotoxic cationic NHC-Au(i) complex to cancer cells. Dalton Trans., 2017, 47(1), 120-126.
[http://dx.doi.org/10.1039/C7DT02616A] [PMID: 29192701]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy