Skip to content
2000
Volume 21, Issue 6
  • ISSN: 1573-4064
  • E-ISSN: 1875-6638

Abstract

Background

This work presents the synthesis of Ru(II)NHC complexes bearing a series of 4-fluorobenzyl group. These complexes have been characterized by a variety of spectroscopic methods (1H NMR, 13C NMR, and FTIR) and by elemental analysis techniques.

Methods

These complexes' antitumor activities against - (human neuroblastoma) and (human colon cancer) were investigated by 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) assay.

Results

The results showed that all the synthesized complexes exhibited significant cytotoxic effect with low IC values 15 ± 0.57, 15.26 ± 0.71, 7.64 ± 0.30, 27.66 ± 0.36 and 14.45 ± 0.84 (µg/mL) respectively.

Conclusion

Furthermore, apoptosis assessed by double labeling with Annexin V-FITC/PI indicated that complexes and can effectively induce apoptosis and inhibit cell proliferation at the S phase in cells. Taken together, Ru(II)NHC complexes containing the 4-fluorobenzyl group have significant potential for the development of novel, highly effective anticancer agents.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/mc/10.2174/0115734064331622241113032042
2025-02-11
2025-09-02

  • From This Site

    /content/journals/mc/10.2174/0115734064331622241113032042
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. HuangJ. StevensE.D. NolanS.P. PetersenJ.L. Olefin metathesis-active ruthenium complexes bearing a nucleophilic carbene ligand.J. Am. Chem. Soc.1999121122674267810.1021/ja9831352
     [Google Scholar]
  2. NelsonD.J. NolanS.P. N-Heterocyclic Carbenes. N-Heterocyclic Carbenes: Effective Tools for Organometallic Synthesis. NolanS.P. Wiley201412410.1002/9783527671229.ch01
     [Google Scholar]
  3. GüzelA. IsıkZ. GökY. Taskin-TokT. AktaşA. N-heterocyclic compounds, in silico molecular docking studies, and in vitro enzyme inhibition effect against acetylcholinesterase inhibitors.Curr. Top. Med. Chem.202323252416242610.2174/1568026623666230614150520 37317917
     [Google Scholar]
  4. EndersD. NiemeierO. HenselerA. Organocatalysis by N-heterocyclic carbenes.Chem. Rev.2007107125606565510.1021/cr068372z 17956132
     [Google Scholar]
  5. Wencel-DelordJ. DrögeT. LiuF. GloriusF. Towards mild metal-catalyzed C–H bond activation.Chem. Soc. Rev.20114094740476110.1039/c1cs15083a 21666903
     [Google Scholar]
  6. TürkerF. Bereketİ. BarutC.D. AktaşA. GökY. New Pd-PEPPSI complexes bearing meta-cyanobenzyl-Substituted NHC: Synthesis, characterization, crystal structure and catalytic activity in direct C–H arylation of (Hetero)arenes with aryl bromides.J. Mol. Struct.2020120512760810.1016/j.molstruc.2019.127608
     [Google Scholar]
  7. TeyssotM.L. JarrousseA.S. ManinM. ChevryA. RocheS. NorreF. BeaudoinC. MorelL. BoyerD. MahiouR. GautierA. Metal-NHC complexes: A survey of anti-cancer properties.Dalton Trans.2009356894690210.1039/b906308k 20449127
     [Google Scholar]
  8. KaraaslanM.G. AktaşA. GürsesC. GökY. AteşB. Chemistry, structure, and biological roles of Au-NHC complexes as TrxR inhibitors.Bioorg. Chem.20209510355210.1016/j.bioorg.2019.103552 31911299
     [Google Scholar]
  9. HagerL.A. MokeschS. KielerC. Alonso-de CastroS. BaierD. RollerA. KandiollerW. KepplerB.K. BergerW. SalassaL. TerenziA. Ruthenium–arene complexes bearing naphthyl-substituted 1,3-dioxoindan-2-carboxamides ligands for G-quadruplex DNA recognition.Dalton Trans.20194832120401204910.1039/C9DT02078K 31292575
     [Google Scholar]
  10. SarıY. GürsesC. CelepciD.B. KeleştemurÜ. AktaşA. YükselŞ. AteşB. GökY. 4-Vinylbenzyl and 2-morpholinoethyl substituted ruthenium (II) complexes: Design, synthesis, and biological evaluation.J. Mol. Struct.2020120212735510.1016/j.molstruc.2019.127355
     [Google Scholar]
  11. GotheY. MarzoT. MessoriL. Metzler-NolteN. Iridium (I) compounds as prospective anticancer agents: Solution chemistry, antiproliferative profiles and protein interactions for a series of iridium (I) N‐heterocyclic carbene complexes.Chemistry20162235124871249410.1002/chem.201601542 27443984
     [Google Scholar]
  12. GürsesC. AktaşA. BalcıoğluS. FadhilahA. GökY. AteşB. Synthesis, characterization, DNA binding and anticancer activities of the imidazolidine-functionalized (NHC)Ru(II) complexes.J. Mol. Struct.2022124713135010.1016/j.molstruc.2021.131350
     [Google Scholar]
  13. SumithaaC. GaneshpandianM. Half-sandwich ruthenium arene complexes bearing clinically approved drugs as ligands: The importance of metal–drug synergism in metallodrug design.Mol. Pharm.20232031453147910.1021/acs.molpharmaceut.2c01027 36802711
     [Google Scholar]
  14. CatalanoA. MaricondaA. SinicropiM.S. CeramellaJ. IacopettaD. SaturninoC. LongoP. Biological activities of ruthenium NHC complexes: An update.Antibiotics (Basel)202312236510.3390/antibiotics12020365 36830276
     [Google Scholar]
  15. MontañaÁ.M. BernalF.J. LorenzoJ. FarnósC. BatallaC. PrietoM.J. MorenoV. AvilésF.X. MesasJ.M. AlegreM.T. Synthesis, characterization and antiproliferative studies of the enantiomers of cis-[(1,2-camphordiamine)dichloro]platinum(II) complexes.Bioorg. Med. Chem.20081641721173710.1016/j.bmc.2007.11.021 18036822
     [Google Scholar]
  16. ZhangJ.J. Abu el MaatyM.A. HoffmeisterH. SchmidtC. MuenznerJ.K. SchobertR. WölflS. OttI. A multitarget gold(I) complex induces cytotoxicity related to aneuploidy in HCT‐116 colorectal carcinoma cells.Angew. Chem. Int. Ed.20205938167951680010.1002/anie.202006212 32529715
     [Google Scholar]
  17. YangZ. HuangS. LiuY. ChangX. LiangY. LiX. XuZ. WangS. LuY. LiuY. LiuW. Biotin-targeted Au (I) radiosensitizer for cancer synergistic therapy by intervening with redox homeostasis and inducing ferroptosis.J. Med. Chem.202265128401841510.1021/acs.jmedchem.2c00300 35687871
     [Google Scholar]
  18. LuY. MaX. ChangX. LiangZ. LvL. ShanM. LuQ. WenZ. GustR. LiuW. Recent development of gold(i) and gold(iii) complexes as therapeutic agents for cancer diseases.Chem. Soc. Rev.202251135518555610.1039/D1CS00933H 35699475
     [Google Scholar]
  19. BianM. FanR. JiangG. WangY. LuY. LiuW. Halo and pseudohalo gold (I)–NHC complexes derived from 4, 5-diarylimidazoles with excellent in vitro and in vivo anticancer activities against HCC.J. Med. Chem.202063179197921110.1021/acs.jmedchem.0c00257 32787098
     [Google Scholar]
  20. ChenQ.M. ZengY. ZhangM.R. JinL. ZhouP. WuX.H. RenW.X. Synthesis and antitumor activity of gold(I) N-heterocyclic carbene with dithiocarbamate and alkynyl complexes.Inorg. Chim. Acta202456812208510.1016/j.ica.2024.122085
     [Google Scholar]
  21. ZhaoQ. HanB. PengC. ZhangN. HuangW. HeG. LiJ.L. A promising future of metal‐ N ‐heterocyclic carbene complexes in medicinal chemistry: The emerging bioorganometallic antitumor agents.Med. Res. Rev.20244452194223510.1002/med.22039 38591229
     [Google Scholar]
  22. ShiQ. JiY. ShiY. ZhaoZ. ZhuW. XuY. LiB. QianX. Floro-pyrazolo[3,4-d]pyrimidine derivative as a novel plant activator induces two-pathway immune system.Phytochemistry202118411265710.1016/j.phytochem.2021.112657 33461047
     [Google Scholar]
  23. ZenginR. GökY. DemirY. ŞenB. Taskin-TokT. AktaşA. DemirciÖ. Gülçinİ. AygünM. Fluorinated benzimidazolium salts: Synthesis, characterization, molecular docking studies and inhibitory properties against some metabolic enzymes.J. Fluor. Chem.202326711009410.1016/j.jfluchem.2023.110094
     [Google Scholar]
  24. BéguéJ.P. Bonnet-DelponD. Bioorganic and Medicinal Chemistry of Fluorine.Hoboken, New JerseyJohn Wiley & Sons200810.1002/9780470281895
     [Google Scholar]
  25. KirschP. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications.Darmstadt, GermanyJohn Wiley & Sons2006
     [Google Scholar]
  26. ZhouY. WangJ. GuZ. WangS. ZhuW. AceñaJ.L. SoloshonokV.A. IzawaK. LiuH. 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.2016116242251810.1021/acs.chemrev.5b00392 26756377
     [Google Scholar]
  27. KondratovI.S. TolmachovaN.A. HaufeG. Diels–alder reaction in the synthesis of fluorinated (hetero)aromatic compounds.Eur. J. Org. Chem.2018201827-283618364710.1002/ejoc.201800327
     [Google Scholar]
  28. TomashenkoO.A. GrushinV.V. Aromatic trifluoromethylation with metal complexes.Chem. Rev.201111184475452110.1021/cr1004293 21456523
     [Google Scholar]
  29. JeschkeP. The unique role of fluorine in the design of active ingredients for modern crop protection.ChemBioChem20045557058910.1002/cbic.200300833 15122630
     [Google Scholar]
  30. HamideM. GökY. DemirY. SevinçekR. Taskin-TokT. TezcanB. AktaşA. Gülçinİ. AygünM. GüzelB. Benzimidazolium salts containing trifluoromethoxybenzyl: Synthesis, characterization, crystal structure, molecular docking studies and enzymes inhibitory properties.Chem. Biodivers.20221912e20220025710.1002/cbdv.202200257 36260838
     [Google Scholar]
  31. HamideM. GökY. DemirY. YakalıG. TokT.T. AktaşA. SevinçekR. GüzelB. Gülçinİ. Pentafluorobenzyl-substituted benzimidazolium salts: Synthesis, characterization, crystal structures, computational studies and inhibitory properties of some metabolic enzymes.J. Mol. Struct.2022126513326610.1016/j.molstruc.2022.133266
     [Google Scholar]
  32. TezcanB. GökY. SevinçekR. TaslimiP. Taskin-TokT. AktaşA. GüzelB. AygünM. Gülçinİ. Benzimidazolium salts bearing the trifluoromethyl group as organofluorine compounds: Synthesis, characterization, crystal structure, in silico study, and inhibitory profiles against acetylcholinesterase and α‐glycosidase.J. Biochem. Mol. Toxicol.2022364e2300110.1002/jbt.23001 35225413
     [Google Scholar]
  33. BalS. DemirciÖ. ŞenB. TaşkınT.T. TaslimiP. AktaşA. GökY. AygünM. Gülçinİ. Silver N‐heterocyclic carbene complexes bearing fluorinated benzyl group: Synthesis, characterization, crystal structure, computational studies, and inhibitory properties against some metabolic enzymes.Appl. Organomet. Chem.2021359e631210.1002/aoc.6312
     [Google Scholar]
  34. TwentymanP.R. LuscombeM. A study of some variables in a tetrazolium dye (MTT) based assay for cell growth and chemosensitivity.Br. J. Cancer198756327928510.1038/bjc.1987.190 3663476
     [Google Scholar]
  35. HuangC. ZhangH. YangY. LiuH. ChenJ. WangY. LiangL. HuH. LiuY. Synthesis, characterization, molecular docking, RNA-sequence and anticancer efficacy evaluation in vitro of ruthenium(II) complexes on B16 cells.J. Inorg. Biochem.202324711232910.1016/j.jinorgbio.2023.112329 37478780
     [Google Scholar]
  36. MosmannT. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays.J. Immunol. Methods1983651-2556310.1016/0022‑1759(83)90303‑4 6606682
     [Google Scholar]
  37. AktaşA. GökY. 4-Vinylbenzyl-substituted silver(I) N-heterocyclic carbene complexes and ruthenium(II) N-heterocyclic carbene complexes: Synthesis and transfer hydrogenation of ketones.Trans. Met. Chem. (Weinh.)201439892593110.1007/s11243‑014‑9877‑y
     [Google Scholar]
  38. SadoughiF. HallajzadehJ. AsemiZ. MansourniaM.A. AlemiF. YousefiB. Signaling pathways involved in cell cycle arrest during the DNA breaks.DNA Repair (Amst.)20219810304710.1016/j.dnarep.2021.103047 33454524
     [Google Scholar]
  39. WangX. LuX. ZhuR. ZhangK. LiS. ChenZ. LiL. Betulinic acid induces apoptosis in differentiated PC12 cells via ROS-mediated mitochondrial pathway.Neurochem. Res.20174241130114010.1007/s11064‑016‑2147‑y 28124213
     [Google Scholar]
  40. JanR. ChaudhryG.S. Understanding apoptosis and apoptotic pathways targeted cancer therapeutics.Adv. Pharm. Bull.20199220521810.15171/apb.2019.024 31380246
     [Google Scholar]
  41. ZecM. Srdic-RajicT. KrivokucaA. JankovicR. TodorovicT. AndelkovicK. RadulovicS. Novel selenosemicarbazone metal complexes exert anti-tumor effect via alternative, caspase-independent necroptotic cell death.Med. Chem.201410875977110.2174/1573406410666140327122009 24678785
     [Google Scholar]
/content/journals/mc/10.2174/0115734064331622241113032042
Loading
Design, Synthesis, Characterization, and Antitumor Activities of Benzimidazole-functionalized Organoruthenium Complexes Bearing Fluorine Group
Med. Chem. 21, 546 (2025); https://doi.org/10.2174/0115734064331622241113032042
/content/journals/mc/10.2174/0115734064331622241113032042
/content/journals/mc/10.2174/0115734064331622241113032042
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.

file format download Download

  • Article Type:     Research Article
Keyword(s): Antitumor activity; benzimidazole; DNA binding; N-heterocyclic carbenes; organometallic; ruthenium

Most Cited Most Cited RSS feed

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