Skip to content
2000
Volume 25, Issue 16
  • ISSN: 1389-5575
  • E-ISSN: 1875-5607

Abstract

Quinoxalines are a versatile class of nitrogen-containing heterocyclic compounds that have been extensively studied for their diverse pharmacological properties. Recently, interest has grown in exploring quinoxaline derivatives for applications in oral health, driven by their unique mechanisms of action and potential to address major challenges in dental medicine. This review comprehensively examines the recent progress in the development of quinoxaline-based compounds targeting oral pathogens responsible for dental caries, periodontitis, and other biofilm-associated diseases. Beyond their antimicrobial effects, quinoxalines also exhibit anti-inflammatory properties by modulating key molecular pathways implicated in periodontal inflammation, thereby offering a dual therapeutic potential. Moreover, their incorporation as functional additives in restorative dental materials is emerging, aiming to enhance antimicrobial efficacy and improve material performance. Despite promising and data, several critical barriers must be overcome before clinical translation can be realized. These include ensuring biocompatibility with oral tissues, achieving formulation stability under the dynamic conditions within the oral environment, and optimizing delivery systems to ensure targeted, sustained release at the site of action. This review highlights current strategies to address these challenges and proposes directions for future research, including advanced formulation technologies and comprehensive preclinical evaluations. Ultimately, quinoxaline derivatives hold significant promise as multifunctional agents capable of integrating antimicrobial, anti-inflammatory, and biomaterial-enhancing properties to improve oral health outcomes. This synthesis of current knowledge supports continued investigation into quinoxalines as novel therapeutics and functional components for dental care.

Loading

Article metrics loading...

/content/journals/mrmc/10.2174/0113895575415392250904071753
2025-09-15
2025-12-11
Loading full text...

Full text loading...

References

  1. PyszkaI. JędrzejewskaB. Modification of light-cured composition for permanent dental fillings: Mass stability of new composites containing quinoline and quinoxaline derivatives in solutions simulating the oral cavity environment.Materials20241723600310.3390/ma17236003 39685438
    [Google Scholar]
  2. PereiraJ.A. PessoaA.M. CordeiroM.N.D.S. FernandesR. PrudêncioC. NoronhaJ.P. VieiraM. Quinoxaline, its derivatives and applications: A state of the art review.Eur. J. Med. Chem.20159766467210.1016/j.ejmech.2014.06.058 25011559
    [Google Scholar]
  3. FarghalyT.A. AlqurashiR.M. MasaretG.S. AbdulwahabH.G. Recent methods for the synthesis of quinoxaline derivatives and their biological activities.Mini Rev. Med. Chem.202424992098210.2174/0113895575264375231012115026 37885112
    [Google Scholar]
  4. PyszkaI. JędrzejewskaB. Study on new dental materials containing quinoxaline-based photoinitiators.Polymers20241682155
    [Google Scholar]
  5. Oral health2022Available from: https://www.who.int/health-topics/oral-health#tab=tab_1
  6. KuangX. ChenV. XuX. Novel approaches to the control of oral microbial biofilms.BioMed Res. Int.2018201811310.1155/2018/6498932 30687755
    [Google Scholar]
  7. ZhangB. ZhaoM. TianJ. LeiL. HuangR. Novel antimicrobial agents targeting the Streptococcus mutans biofilms discovery through computer technology.Front. Cell. Infect. Microbiol.202212106523510.3389/fcimb.2022.1065235 36530419
    [Google Scholar]
  8. PyszkaI. JędrzejewskaB. Design of dyes based on the quinoline or quinoxaline skeleton towards visible light photoinitiators.Int. J. Mol. Sci.2024258428910.3390/ijms25084289 38673872
    [Google Scholar]
  9. AhammedK.S. PalR. ChakrabortyJ. KanungoA. PurnimaP.S. DuttaS. DNA structural alteration leading to antibacterial properties of 6-nitroquinoxaline derivatives.J. Med. Chem.201962177840785610.1021/acs.jmedchem.9b00599 31390524
    [Google Scholar]
  10. RenZ. CuiT. ZengJ. ChenL. ZhangW. XuX. ChengL. LiM. LiJ. ZhouX. LiY. Molecule targeting glucosyltransferase inhibits Streptococcus mutans biofilm formation and virulence.Antimicrob. Agents Chemother.201660112613510.1128/AAC.00919‑15 26482298
    [Google Scholar]
  11. KumarJ. ChawlaG. KumarU. SahuK. Design and syntheses of some new quinoxaline derivatives containing pyrazoline residue as potential antimicrobial agents.Med. Chem. Res.20142393929394010.1007/s00044‑014‑0976‑2
    [Google Scholar]
  12. ChengG. LiB. WangC. ZhangH. LiangG. WengZ. HaoH. WangX. LiuZ. DaiM. WangY. YuanZ. Systematic and molecular basis of the antibacterial action of quinoxaline 1,4-di-N-oxides against Escherichia coli.PLoS One2015108013645010.1371/journal.pone.0136450 26296207
    [Google Scholar]
  13. El-AtawyM.A. HamedE.A. AlhadiM. OmarA.Z. Synthesis and antimicrobial activity of some new substituted quinoxalines.Molecules20192422419810.3390/molecules24224198 31752396
    [Google Scholar]
  14. AlfadilA. IbrahemK.A. AlrabiaM.W. MokhtarJ.A. AhmedH. The fungicidal effectiveness of 2-chloro-3-hydrazinylquinoxaline against Candida species.PLoS One2024195030337310.1371/journal.pone.0303373 38728271
    [Google Scholar]
  15. IshikawaH. SugiyamaT. YokoyamaA. Synthesis of 2,3-bis(halomethyl)quinoxaline derivatives and evaluation of their antibacterial and antifungal activities.Chem. Pharm. Bull.201361443844410.1248/cpb.c12‑01061 23546003
    [Google Scholar]
  16. RanaM. FaizanM.I. DarS.H. AhmadT. Rahisuddin, Design and synthesis of carbothioamide/carboxamide-based pyrazoline analogs as potential anticancer agents: Apoptosis, molecular docking, ADME assay, and DNA Binding studies.ACS Omega2022726226392265610.1021/acsomega.2c02033 35811873
    [Google Scholar]
  17. MachadoV. CenciA.R. TeixeiraK.F. SensL. TizzianiT. NunesR.J. FerreiraL.L.G. YunesR.A. SandjoL.P. AndricopuloA.D. de OliveiraA.S. Pyrazolines as potential anti-Alzheimer’s agents: DFT, molecular docking, enzyme inhibition and pharmacokinetic studies.RSC Med. Chem.202213121644165610.1039/D2MD00262K 36561075
    [Google Scholar]
  18. AlyM. An insight into the therapeutic impact of quinoxaline derivatives: Recent advances in biological activities (2020–2024).Results Chem.20251310198910.1016/j.rechem.2024.101989
    [Google Scholar]
  19. ElfadilA. AlzahraniA.M. AbdullahH. AlsamhanH. AbujamelT.S. AhmedH.E. Jiman-FataniA. Evaluation of the antibacterial activity of quinoxaline derivative compound against methicillin-resistant Staphylococcus aureus.Infect. Drug Resist.2023162291229610.2147/IDR.S401371 37095779
    [Google Scholar]
  20. MokhtarJ.A. AttallahD. AlquarniM.A. EkhmimiT. SalehB.H. NiyaziH.A. unveiling the efficacy of 3-hydrazinoquinoxaline-2-thiol against Pseudomonas aeruginosa.Bahrain Med. Bull.20254711520
    [Google Scholar]
  21. IbrahemK. AlhazmiW. NiyaziH.A. NiyaziH.A. SalehB. EkhmimiT. MokhtarJ.A. AttallahD. BazuhairM. AlkuwaityK. SaitA. MufrrihM. IsmailM. AlmoghrabiY. DaghistaniH. AlharbiO. AltaybH. AlfadilA. An in vitro investigation of the potential synergistic effect of 3-Hydrazinoquinoxaline-2-Thiol and Thymoquinone’s against Methicillin resistant Staphylococcus aureus (MRSA).J. Pure Appl. Microbiol.20241842837284910.22207/JPAM.18.4.55
    [Google Scholar]
  22. BurgueteA. PontikiE. Hadjipavlou-LitinaD. AncizuS. VillarR. SolanoB. MorenoE. TorresE. PérezS. AldanaI. MongeA. Synthesis and biological evaluation of new quinoxaline derivatives as antioxidant and anti-inflammatory agents.Chem. Biol. Drug Des.201177425526710.1111/j.1747‑0285.2011.01076.x 21244639
    [Google Scholar]
  23. AhmedE.A. MohamedM.F.A. OmranO.A. Novel quinoxaline derivatives as dual EGFR and COX-2 inhibitors: Synthesis, molecular docking and biological evaluation as potential anticancer and anti-inflammatory agents.RSC Advances20221239252042521610.1039/D2RA04498F 36199335
    [Google Scholar]
  24. NeriJ.M. SiqueiraP.E.A. OliveiraA.L.C.S.L. AraújoR.M. Araújo JúniorR.F. MartinsA.A. MarquesI.L. SilvaR.A. AraújoA.A. MenezesF.G. Anticancer, anti-inflammatory and analgesic activities of aminoalcohol-based quinoxaline small molecules.Acta Cir. Bras.20243939512410.1590/acb395124 39109780
    [Google Scholar]
  25. PyszkaI. JędrzejewskaB. Acenaphthoquinoxaline derivatives as dental photoinitiators of acrylates polymerization.Materials20211417488110.3390/ma14174881 34500971
    [Google Scholar]
  26. DumurF. Recent advances on quinoxaline-based photoini-tiators of polymerization.Catalysts202313471810.3390/catal13040718
    [Google Scholar]
  27. ChenL. ChenW. YuY. YangJ. JiangQ. WuW. YangD. Effect of chlorhexidine-loaded poly(amido amine) dendrimer on matrix metalloproteinase activities and remineralization in etched human dentin in vitro.J. Mech. Behav. Biomed. Mater.202112110462510.1016/j.jmbbm.2021.104625 34130080
    [Google Scholar]
  28. VitorinoC. SousaJ. PaisA. Overcoming the oral cavity barriers to treat periodontal disease: Nanoparticles-based drug delivery systems.Int. J. Nanomedicine2012714691482
    [Google Scholar]
  29. RezakhaniL. GharibshahianM. SalehiM. ZamaniS. AbpeikarZ. GhaderzadehO. AlizadehM. MasoudiA. RezaeiN. CheraghaliD. Recent advances in hydrogels applications for tissue engineering and clinical trials.Regen. Ther.20242663564510.1016/j.reth.2024.08.015 39281106
    [Google Scholar]
  30. ScaliaS. MezzenaM. Incorporation of quercetin in lipid microparticles: Effect on photo- and chemical-stability.J. Pharm. Biomed. Anal.2009491909410.1016/j.jpba.2008.10.011 19042102
    [Google Scholar]
  31. ZhangY. JiangR. LeiL. YangY. HuT. Drug delivery systems for oral disease applications.J. Appl. Oral Sci.2022302021034910.1590/1678‑7757‑2021‑0349 35262595
    [Google Scholar]
  32. KimY. ZharkinbekovZ. RaziyevaK. TabyldiyevaL. BerikovaK. ZhumagulD. TemirkhanovaK. SaparovA. Chitosan-based biomaterials for tissue regeneration.Pharmaceutics202315380710.3390/pharmaceutics15030807 36986668
    [Google Scholar]
  33. LuM. GeY. QiuJ. ShaoD. ZhangY. BaiJ. ZhengX. ChangZ. WangZ. DongW. TangC. Redox/pH dual-controlled release of chlorhexidine and silver ions from biodegradable mesoporous silica nanoparticles against oral biofilms.Int. J. Nanomedicine2018137697770910.2147/IJN.S181168 30538453
    [Google Scholar]
  34. HuangC.Y. HuangT.H. KaoC.T. WuY.H. ChenW.C. ShieM.Y. Mesoporous calcium silicate nanoparticles with drug delivery and odontogenesis properties.J. Endod.2017431697610.1016/j.joen.2016.09.012 27939733
    [Google Scholar]
  35. PriyadarshiniB.M. MitaliK. LuT.B. HandralH.K. DubeyN. FawzyA.S. PLGA nanoparticles as chlorhexidine-delivery carrier to resin-dentin adhesive interface.Dent. Mater.201733783084610.1016/j.dental.2017.04.015 28506608
    [Google Scholar]
  36. HuF. ZhouZ. XuQ. FanC. WangL. RenH. XuS. JiQ. ChenX. A novel pH-responsive quaternary ammonium chitosan-liposome nanoparticles for periodontal treatment.Int. J. Biol. Macromol.20191291113111910.1016/j.ijbiomac.2018.09.057 30218737
    [Google Scholar]
  37. ShresthaS. KishenA. Temporal-controlled bioactive molecules releasing core-shell nano-system for tissue engineering strategies in endodontics.Nanomedicine201918112010.1016/j.nano.2019.02.013 30844574
    [Google Scholar]
  38. ChenW. ZhiM. FengZ. GaoP. YuanY. ZhangC. WangY. DongA. Sustained co-delivery of ibuprofen and basic fibroblast growth factor by thermosensitive nanoparticle hydrogel as early local treatment of peri-implantitis.Int. J. Nanomedicine2019141347135810.2147/IJN.S190781 30863065
    [Google Scholar]
  39. TanJ. ZhangM. HaiZ. WuC. LinJ. KuangW. TangH. HuangY. ChenX. LiangG. Sustained release of two bioactive factors from supramolecular hydrogel promotes periodontal bone regeneration.ACS Nano20191355616562210.1021/acsnano.9b00788 31059238
    [Google Scholar]
  40. PanJ. DengJ. LuoY. YuL. ZhangW. HanX. YouZ. LiuY. Thermosensitive hydrogel delivery of human periodontal stem cells overexpressing platelet-derived growth factor-bb enhances alveolar bone defect repair.Stem Cells Dev.201928241620163110.1089/scd.2019.0184 31663419
    [Google Scholar]
  41. HeX.T. LiX. XiaY. YinY. WuR.X. SunH.H. ChenF.M. Building capacity for macrophage modulation and stem cell recruitment in high-stiffness hydrogels for complex periodontal regeneration: Experimental studies in vitro and in rats.Acta Biomater.20198816218010.1016/j.actbio.2019.02.004 30735811
    [Google Scholar]
  42. SilvaC.R. BaboP.S. GulinoM. CostaL. OliveiraJ.M. Silva-CorreiaJ. DominguesR.M.A. ReisR.L. GomesM.E. Injectable and tunable hyaluronic acid hydrogels releasing chemotactic and angiogenic growth factors for endodontic regeneration.Acta Biomater.20187715517110.1016/j.actbio.2018.07.035 30031163
    [Google Scholar]
  43. YadlapatiM. BiguettiC. CavallaF. NievesF. BesseyC. BohluliP. GarletG.P. LetraA. FakhouriW.D. SilvaR.M. Characterization of a vascular endothelial growth factor-loaded bioresorbable delivery system for pulp regeneration.J. Endod.2017431778310.1016/j.joen.2016.09.022 27939739
    [Google Scholar]
/content/journals/mrmc/10.2174/0113895575415392250904071753
Loading
/content/journals/mrmc/10.2174/0113895575415392250904071753
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keyword(s): anti-inflammatory; antimicrobial; biomaterial; oral health; Quinoxaline; quinoxalines
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