Skip to content
2000
image of Selected Metal (Au, Ag, and Cu) Complexes of N-heterocyclic Ligands as Potential Anticancer Agents: A Review

Abstract

Nitrogen-based organic heterocyclic compounds are an important source of therapeutic agents. About 75% of drugs approved by the FDA and currently available in the market are N-heterocyclic organic compounds. The N-heterocyclic organic compounds like pyridine, indole, triazoles, triazine, imidazoles, benzimidazoles, quinazolines, pyrazoles, quinolines, pyrimidines, porphyrin, . have demonstrated significant biological activities. These heterocyclic organic compounds also coordinate with various metal ions and form coordination compounds. Most of them have shown improved biological activities. The research on the metal complexes of these compounds reported their significant biological activities. N-heterocyclic-based metal complexes showed outstanding anticancer activities against different cancer cell lines, including VEGFR-2, HT-29, MDA-MB-231, MCF-7 K562, A549, HepG2, HL60, A2780, WI-38, Colo-205, PC-3, and other cancer cell lines. Some of these compounds showed better anticancer activity than cisplatin. In this review, we summarized the anticancer properties of N-heterocyclic-based gold (Au), silver (Ag), and copper (Cu) complexes and explored the mechanisms of action and potential structure-activity relationships (SAR) of these complexes. Our goal is to assist researchers in designing highly potent N-heterocyclic-based Au, Ag, and Cu complexes for the potential treatment of various cancers.

Loading

Article metrics loading...

/content/journals/acamc/10.2174/0118715206331002241119145651
2025-01-03
2025-04-02
Loading full text...

Full text loading...

References

  1. Al-Saidi H.M. Khan S. A review on organic fluorimetric and colorimetric chemosensors for the detection of Ag(I) ions. Crit. Rev. Anal. Chem. 2022 52 1 18 10.1080/10408347.2022.2133561 36251012
    [Google Scholar]
  2. Khan S. Alhumaydhi F.A. Ibrahim M.M. Alqahtani A. Alshamrani M. Alruwaili A.S. Hassanian A.A. Khan S. Recent advances and therapeutic journey of schiff base complexes with selected metals (Pt, Pd, Ag, Au) as potent anticancer agents: A review. Anticancer. Agents Med. Chem. 2022 22 18 3086 3096 10.2174/1871520622666220511125600 35546764
    [Google Scholar]
  3. Khan S. Chen X. Almahri A. Allehyani E.S. Alhumaydhi F.A. Ibrahim M.M. Ali S. Recent developments in fluorescent and colorimetric chemosensors based on schiff bases for metallic cations detection: A review. J. Environ. Chem. Eng. 2021 9 6 106381 10.1016/j.jece.2021.106381
    [Google Scholar]
  4. Khan S. Muhammad M. Al-Saidi H.M. Hassanian A.A. Alharbi W. Alharbi K.H. Synthesis, characterization and applications of schiff base chemosensor for determination of Cu2+ ions. J. Saudi Chem. Soc. 2022 26 4 101503 10.1016/j.jscs.2022.101503
    [Google Scholar]
  5. Mohammad Abu-Taweel G. Ibrahim M.M. Khan S. Al-Saidi H.M. Alshamrani M. Alhumaydhi F.A. Alharthi S.S. Medicinal importance and chemosensing applications of pyridine derivatives: A review. Crit. Rev. Anal. Chem. 2022 54 3 599 616 10.1080/10408347.2022.2089839 35724248
    [Google Scholar]
  6. Kerru N. Gummidi L. Maddila S. Gangu K.K. Jonnalagadda S.B. 2020 A review on recent advances in nitrogen-containing molecules and their biological applications. Molecules 1909 25 8 10.3390/molecules25081909
    [Google Scholar]
  7. Alrooqi M. Khan S. Alhumaydhi F.A. Asiri S.A. Alshamrani M. Mashraqi M.M. Alzamami A. Alshahrani A.M. Aldahish A.A. A therapeutic journey of pyridine-based heterocyclic compounds as potent anticancer agents: A review (from 2017 to 2021). Anticancer. Agents Med. Chem. 2022 22 15 2775 2787 10.2174/1871520622666220324102849 35331100
    [Google Scholar]
  8. Chiacchio M.A. Iannazzo D. Romeo R. Giofrè S.V. Legnani L. Pyridine and pyrimidine derivatives as privileged scaffolds in biologically active agents. Curr. Med. Chem. 2020 26 40 7166 7195 10.2174/0929867325666180904125400 30182842
    [Google Scholar]
  9. Nural Y. Ozdemir S. Yalcin M.S. Demir B. Atabey H. Seferoglu Z. Ece A. New bis- and tetrakis-1,2,3-triazole derivatives: Synthesis, DNA cleavage, molecular docking, antimicrobial, antioxidant activity and acid dissociation constants. Bioorg. Med. Chem. Lett. 2022 55 128453 10.1016/j.bmcl.2021.128453 34801684
    [Google Scholar]
  10. Xu H. Lv M. Developments of indoles as anti-HIV-1 inhibitors. Curr. Pharm. Des. 2009 15 18 2120 2148 10.2174/138161209788489168 19519449
    [Google Scholar]
  11. Küçükgüzel G. Çikla-Süzgün P. 2015 Recent advances bioactive 1,2,4-triazole-3-thiones. Eur. J. Med. Chem. 830 870 97 10.1016/j.ejmech.2014.11.033
    [Google Scholar]
  12. Gaba M. Mohan C. 2015 Development of drugs based on imidazole and benzimidazole bioactive heterocycles: Recent advances and future directions. Med. Chem. Res. 25 173 210 10.1007/s00044‑015‑1495‑5
    [Google Scholar]
  13. Kadhim M.I. Husein I. Pharmaceutical and biological application of new synthetic compounds of pyranone, pyridine, pyrmidine, pyrazole and isoxazole incorporating on 2-flouroquinoline moieties. Syst. Rev. Pharm. 2020 11 2 679 684 10.5530/SRP.2020.2.98
    [Google Scholar]
  14. Faria J.V. Vegi P.F. Miguita A.G.C. dos Santos M.S. Boechat N. Bernardino A.M.R. 2017 Recently reported biological activities of pyrazole compounds. Bioorg. Med. Chem. 25 21 5891 5903 10.1016/j.bmc.2017.09.035
    [Google Scholar]
  15. Omar A. Saleh N.M. Abdel-Rahman A.A-H. El-Adl K. Review article; Anticancer activities of some fused heterocyclic moieties containing nitrogen and/or sulfur heteroatoms. Al-Azhar J. Pharm. Sci. 2020 62 2 39 54 10.21608/ajps.2020.118375
    [Google Scholar]
  16. Ma D.L. Wu C. Wu K.J. Leung C.H. Iridium(III) complexes targeting apoptotic cell death in cancer cells. Molecules 24 15 2739 2019 10.3390/molecules24152739
    [Google Scholar]
  17. Katsaros N. Anagnostopoulou A. Rhodium and its compounds as potential agents in cancer treatment. Crit. Rev. Oncol. Hematol. 2002 42 3 297 308 10.1016/S1040‑8428(01)00222‑0 12050021
    [Google Scholar]
  18. D’Amato A. Mariconda A. Iacopetta D. Ceramella J. Catalano A. Sinicropi M.S. Longo P. Complexes of ruthenium(II) as promising dual-active agents against cancer and viral infections. Pharmaceuticals (Basel) 2023 1729 16 12 10.3390/ph16121729
    [Google Scholar]
  19. Zhang C. Xu C. Gao X. Yao Q. Platinum-based drugs for cancer therapy and anti-tumor strategies. Theranostics 2022 12 5 2115 2132 10.7150/thno.69424 35265202
    [Google Scholar]
  20. Ma D.L. Wang M. Mao Z. Yang C. Ng C.T. Leung C.H. Rhodium complexes as therapeutic agents. Dalton Trans. 2016 45 7 2762 2771 10.1039/C5DT04338G 26743935
    [Google Scholar]
  21. Jin S. Guo Y. Guo Z. Wang X. Monofunctional platinum(II) anticancer agents. Pharmaceuticals (Basel) 14 2 2021 133 10.3390/ph14020133
    [Google Scholar]
  22. Tan S.J. Yan Y.K. Lee P.P.F. Lim K.H. Copper, gold and silver compounds as potential new anti-tumor metallodrugs. Future Med. Chem. 2010 2 10 1591 1608 10.4155/fmc.10.234 21426151
    [Google Scholar]
  23. Medici S. Peana M. Nurchi V.M. Lachowicz J.I. Crisponi G. Zoroddu M.A. Noble metals in medicine: Latest advances. Coord. Chem. Rev. 2015 284 329 350 10.1016/j.ccr.2014.08.002
    [Google Scholar]
  24. Vechalapu S.K. Kumar R. Sachan S.K. Shaikh K. Mahapatra A.D. Draksharapu A. Allimuthu D. Copper and manganese complexes of pyridinecarboxaldimine induce oxidative cell death in cancer cells. ACS Appl. Bio Mater. 2024 7 10 6696 6705 10.1021/acsabm.4c00854 39240687
    [Google Scholar]
  25. Kalarani R. Sankarganesh M. Kumar G.G.V. Kalanithi M. Synthesis, spectral, DFT calculation, sensor, antimicrobial and DNA binding studies of Co(II), Cu(II) and Zn(II) metal complexes with 2-amino benzimidazole Schiff base. J. Mol. Struct. 2020 1206 127725 10.1016/j.molstruc.2020.127725
    [Google Scholar]
  26. Sankarganesh M. Vijay Solomon R. Dhaveethu Raja J. Platinum complex with pyrimidine- and morpholine-based ligand: Synthesis, spectroscopic, DFT, TDDFT, catalytic reduction, in vitro anticancer, antioxidant, antimicrobial, dna binding and molecular modeling studies. J. Biomol. Struct. Dyn. 2020 ••• 10.1080/07391102.2020.1727364 32036758
    [Google Scholar]
  27. Yellol J. Pérez S.A. Buceta A. Yellol G. Donaire A. Szumlas P. Bednarski P.J. Makhloufi G. Janiak C. Espinosa A. Ruiz J. Novel C. Novel C,N-Cyclometalated benzimidazole ruthenium(II) and iridium(III) complexes as antitumor and antiangiogenic agents: A structure-activity relationship study. J. Med. Chem. 2015 58 18 7310 7327 10.1021/acs.jmedchem.5b01194 26313136
    [Google Scholar]
  28. El-Boraey H.A. Emam S.M. Tolan D.A. El-Nahas A.M. Structural studies and anticancer activity of a novel (N6O4) macrocyclic ligand and its Cu(II) complexes. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2011 78 1 360 370 10.1016/j.saa.2010.10.021 21081283
    [Google Scholar]
  29. Shen K. Han X. Li C. Huang G. Mao S. Shi X. Wu H. 2018 Synthesis, structure, electrochemical properties, and antioxidant activities of copper(II) and zinc(II) complexes with N,N-bis(N-ethyl-2-ylmethylbenzimidazol)allylamine ligand. J. Coord. Chem. 71 7 980 990 10.1080/00958972.2018.1454593
    [Google Scholar]
  30. Kesavan M.P. Vinoth Kumar G.G. Dhaveethu Raja J. Anitha K. Karthikeyan S. Rajesh J. DNA interaction, antimicrobial, antioxidant and anticancer studies on Cu(II) complexes of Luotonin A. J. Photochem. Photobiol. B 2017 167 20 28 10.1016/j.jphotobiol.2016.11.024 28039786
    [Google Scholar]
  31. Kanthecha D.A. Bhatt B.S. Patel M.N. Synthesis, characterization and biological activities of imidazo[1,2-a]pyridine based gold(III) metal complexes. Heliyon 2019 5 6 e01968 10.1016/j.heliyon.2019.e01968 31294115
    [Google Scholar]
  32. Rubbiani R. Zehnder T.N. Mari C. Blacque O. Venkatesan K. Gasser G. Anticancer profile of a series of gold(III) (2-phenyl)pyridine complexes. ChemMedChem 2014 9 12 2781 2790 10.1002/cmdc.201402446 25377650
    [Google Scholar]
  33. Trommenschlager A. Chotard F. Bertrand B. Amor S. Dondaine L. Picquet M. Richard P. Bettaïeb A. Le Gendre P. Paul C. Goze C. Bodio E. Gold(i)–BODIPY–imidazole bimetallic complexes as new potential anti-inflammatory and anticancer trackable agents. Dalton Trans. 2017 46 25 8051 8056 10.1039/C7DT01377A 28594007
    [Google Scholar]
  34. Serratice M. Bertrand B. Janssen E.F.J. Hemelt E. Zucca A. Cocco F. Cinellu M.A. Casini A. Gold(i) compounds with lansoprazole-type ligands: Synthesis, characterization and anticancer properties in vitro. MedChemComm 2014 5 9 1418 1422 10.1039/C4MD00241E
    [Google Scholar]
  35. Turek J. Růžičková Z. Tloušťová E. Mertlíková-Kaiserová H. Günterová J. Rulíšek L. Růžička A. 1,2,4‐Triazole‐based N ‐heterocyclic carbene complexes of gold(I): Synthesis, characterization and biological activity. Appl. Organomet. Chem. 2016 30 5 318 322 10.1002/aoc.3434
    [Google Scholar]
  36. Sankarganesh M. Dhaveethu Raja J. Sakthikumar K. Solomon R.V. Rajesh J. Athimoolam S. Vijayakumar V. New bio-sensitive and biologically active single crystal of pyrimidine scaffold ligand and its gold and platinum complexes: DFT, antimicrobial, antioxidant, DNA interaction, molecular docking with DNA/BSA and anticancer studies. Bioorg. Chem. 2018 81 144 156 10.1016/j.bioorg.2018.08.006 30121002
    [Google Scholar]
  37. Sankarganesh M. Raja J.D. Revathi N. Solomon R.V. Kumar R.S. Gold(III) complex from pyrimidine and morpholine analogue Schiff base ligand: Synthesis, characterization, DFT, TDDFT, catalytic, anticancer, molecular modeling with DNA and BSA and DNA binding studies. J. Mol. Liq. 2019 294 111655 10.1016/j.molliq.2019.111655
    [Google Scholar]
  38. Sun R.W.Y. Lok C.N. Fong T.T.H. Li C.K.L. Yang Z.F. Zou T. Siu A.F-M. Che C-M. A dinuclear cyclometalated gold(iii)–phosphine complex targeting thioredoxin reductase inhibits hepatocellular carcinoma in vivo. Chem. Sci. (Camb.) 2013 4 5 1979 1988 10.1039/c3sc21972k
    [Google Scholar]
  39. Cuin A. Massabni A.C. Pereira G.A. Leite C.Q.F. Pavan F.R. Sesti-Costa R. Heinrich T.A. Costa-Neto C.M. 6-Mercaptopurine complexes with silver and gold ions: Anti-tuberculosis and anti-cancer activities. Biomed. Pharmacother. 2011 65 5 334 338 10.1016/j.biopha.2011.04.012 21775091
    [Google Scholar]
  40. Maiore L. Cinellu M.A. Nobili S. Landini I. Mini E. Gabbiani C. Messori L. Gold(III) complexes with 2-substituted pyridines as experimental anticancer agents: Solution behavior, reactions with model proteins, antiproliferative properties. J. Inorg. Biochem. 2012 108 123 127 10.1016/j.jinorgbio.2011.11.007 22173093
    [Google Scholar]
  41. Ali K.A. Abd-Elzaher M.M. Mahmoud K. Synthesis and anticancer properties of silver(I) complexes containing 2,6-bis(substituted)pyridine derivatives. Int. J. Med. Chem. 2013 2013 1 7 10.1155/2013/256836 25386361
    [Google Scholar]
  42. Li S.X. Chen Y.F. Lu Y. Xu S.H. Liao B.L. Synthesis, fluorescence, and anticancer activity of silver (I) complex based on 2-hydroxyquinoxaline ligand. Inorg. Nano-Met. Chem. 2020 50 4 315 320 10.1080/24701556.2020.1711772
    [Google Scholar]
  43. Aulakh J.K. Lobana T.S. Sood H. Arora D.S. Kaur R. Singh J. Garcia-Santos I. Kaur M. Jasinski J.P. Silver derivatives of multi-donor heterocyclic thioamides as antimicrobial/anticancer agents: Unusual bio-activity against methicillin resistant S. aureus, S. epidermidis, and E. faecalis and human bone cancer MG63 cell line. RSC Advances 2019 9 27 15470 15487 10.1039/C9RA01804B 35514853
    [Google Scholar]
  44. Stryjska K. Radko L. Chęcińska L. Kusz J. Posyniak A. Ochocki J. 2020 Synthesis, spectroscopy, light stability, single-crystal analysis, and in vitro cytotoxic activity on HepG2 liver cancer of two novel silver(I) complexes of miconazole. Int. J. Mol. Sci. 21 10 3629 10.3390/ijms21103629
    [Google Scholar]
  45. Li W. Zheng M. Shang Y. Synthesis, characterization, thermal behavior, and antitumor activities of an Ag (I) complex based on 4-(2-hydroxyphenyl)-2-methylpyrimidine. J. Chem. Res. 46 3 2022 10.1177/17475198221103541
    [Google Scholar]
  46. Alshamrani M. Recent advances and therapeutic journey of pyridine-based Cu(II) complexes as potent anticancer agents: A review (2015–2022). J. Coord. Chem. 2023 76 1 1 19 10.1080/00958972.2022.2164190
    [Google Scholar]
  47. Dam J. Ismail Z. Kurebwa T. Gangat N. Harmse L. Marques H.M. Lemmerer A. Bode M.L. de Koning C.B. Synthesis of copper and zinc 2-(pyridin-2-yl)imidazo[1,2-a]pyridine complexes and their potential anticancer activity. Eur. J. Med. Chem. 2017 126 353 368 10.1016/j.ejmech.2016.10.041 27907874
    [Google Scholar]
  48. Geyl K.K. Baykov S.V. Kalinin S.A. Bunev A.S. Troshina M.A. Sharonova T.V. Skripkin M.Y. Kasatkina S.O. Presnukhina S.I. Shetnev A.A. Krasavin M.Y. Boyarskiy V.P. Synthesis, structure, and antiproliferative action of 2-pyridyl urea-based Cu(II) complexes. Biomedicines 2022 10 2 461 10.3390/biomedicines10020461 35203671
    [Google Scholar]
  49. Anjomshoa M. Hadadzadeh H. Torkzadeh-Mahani M. Fatemi S.J. Adeli-Sardou M. Rudbari H.A. Nardo V.M. A mononuclear Cu(II) complex with 5,6-diphenyl-3-(2-pyridyl)-1,2,4-triazine: Synthesis, crystal structure, DNA- and BSA-binding, molecular modeling, and anticancer activity against MCF-7, A-549, and HT-29 cell lines. Eur. J. Med. Chem. 2015 96 66 82 10.1016/j.ejmech.2015.04.020 25874332
    [Google Scholar]
  50. Yuan B. Hu J. Guo Y. Zhang J. Zhang S. Zhang K. Zhao J. Hou H. Nuclei DNA and mitochondria dual damages induced by thiosemicarbazone tripyridyl copper complexes with potential anti-tumor activity. Polyhedron 2021 203 115225 10.1016/j.poly.2021.115225
    [Google Scholar]
  51. Pathaw L. Khamrang T. Selvakumaran B. Murali M. Arul Prakash P. Mohamed Jaabir M.S. Velusamy M. Synthesis, structure, characterization and biological evaluation of 3‐substituted 1‐pyridin‐2‐ylimidazo[1,5‐a]pyridine‐based copper(I)–phosphine complexes for anticancer drug screening. Appl. Organomet. Chem. 2021 35 1 e6025 10.1002/aoc.6025
    [Google Scholar]
  52. Marzano C. Pellei M. Colavito D. Alidori S. Lobbia G.G. Gandin V. Tisato F. Santini C. Synthesis, characterization, and in vitro antitumor properties of tris(hydroxymethyl)phosphine copper(I) complexes containing the new bis(1,2,4-triazol-1-yl)acetate ligand. J. Med. Chem. 2006 49 25 7317 7324 10.1021/jm0601248 17149861
    [Google Scholar]
  53. Shaikh S.A. Bhat S.S. Hegde P.L. Revankar V.K. Kate A. Kirtani D. Kumbhar A.A. Kumbar V. Bhat K. Synthesis, structural characterization, protein binding, DNA cleavage and anticancer activity of fluorophore labelled copper(ii) complexes based on 1,8-naphthalimide conjugates. New J. Chem. 2021 45 35 16319 16332 10.1039/D1NJ02696H
    [Google Scholar]
  54. Prosser K.E. Chang S.W. Saraci F. Le P.H. Walsby C.J. Anticancer copper pyridine benzimidazole complexes: ROS generation, biomolecule interactions, and cytotoxicity. J. Inorg. Biochem. 2017 167 89 99 10.1016/j.jinorgbio.2016.11.006 27915178
    [Google Scholar]
  55. Hou L. Jia X. Wu Y. Li J. Yao D. Gou Y. Huang G. Aroylhydrazone Cu(Ⅱ) complexes: Syntheses, crystal structures, and anticancer properties. J. Mol. Struct. 2021 1239 130469 10.1016/j.molstruc.2021.130469
    [Google Scholar]
  56. Rodić M.V. Leovac V.M. Jovanović L.S. Spasojević V. Joksović M.D. Stanojković T. Matić I.Z. Vojinović-Ješić L.S. Marković V. Synthesis, characterization, cytotoxicity and antiangiogenic activity of copper(II) complexes with 1-adamantoyl hydrazone bearing pyridine rings. Eur. J. Med. Chem. 2016 115 75 81 10.1016/j.ejmech.2016.03.003 27084495
    [Google Scholar]
  57. Pan R.K. Song J.L. Li G.B. Lin S.Q. Liu S.G. Yang G.Z. 2017 Copper(II), cobalt(II) and zinc(II) complexes based on a tridentate bis(benzimidazole)pyridine ligand: Synthesis, crystal structures, electrochemical properties and antitumour activities. Transit. Met. Chem. 42 253 262 10.1007/s11243‑017‑0129‑9
    [Google Scholar]
  58. Choroba K. Machura B. Szlapa-Kula A. Malecki J.G. Raposo L. Roma-Rodrigues C. Cordeiro S. Baptista P.V. Fernandes A.R. Square planar Au(III), Pt(II) and Cu(II) complexes with quinoline-substituted 2,2′:6′,2″-terpyridine ligands: From in vitro to in vivo biological properties. Eur. J. Med. Chem. 2021 218 113404 10.1016/j.ejmech.2021.113404 33823390
    [Google Scholar]
/content/journals/acamc/10.2174/0118715206331002241119145651
Loading
/content/journals/acamc/10.2174/0118715206331002241119145651
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keywords: N-heterocyclic compounds ; cisplatin ; metal complexes ; anticancer activity
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test