Skip to content
2000
image of Quinoxalines in Oral Health: From Antimicrobials to Biomaterials

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.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/mrmc/10.2174/0113895575415392250904071753
2025-09-15
2025-10-19

  • From This Site

    /content/journals/mrmc/10.2174/0113895575415392250904071753
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Pyszka I. Jędrzejewska B. 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. Materials 2024 17 23 6003 10.3390/ma17236003 39685438
    [Google Scholar]
  2. Pereira J.A. Pessoa A.M. Cordeiro M.N.D.S. Fernandes R. Prudêncio C. Noronha J.P. Vieira M. Quinoxaline, its derivatives and applications: A state of the art review. Eur. J. Med. Chem. 2015 97 664 672 10.1016/j.ejmech.2014.06.058 25011559
    [Google Scholar]
  3. Farghaly T.A. Alqurashi R.M. Masaret G.S. Abdulwahab H.G. Recent methods for the synthesis of quinoxaline derivatives and their biological activities. Mini Rev. Med. Chem. 2024 24 9 920 982 10.2174/0113895575264375231012115026 37885112
    [Google Scholar]
  4. Pyszka I. Jędrzejewska B. Study on new dental materials containing quinoxaline-based photoinitiators. Polymers 2024 16 8 2155
    [Google Scholar]
  5. Oral health 2022 Available from: https://www.who.int/health-topics/oral-health#tab=tab_1
  6. Kuang X. Chen V. Xu X. Novel approaches to the control of oral microbial biofilms. BioMed Res. Int. 2018 2018 1 13 10.1155/2018/6498932 30687755
    [Google Scholar]
  7. Zhang B. Zhao M. Tian J. Lei L. Huang R. Novel antimicrobial agents targeting the Streptococcus mutans biofilms discovery through computer technology. Front. Cell. Infect. Microbiol. 2022 12 1065235 10.3389/fcimb.2022.1065235 36530419
    [Google Scholar]
  8. Pyszka I. Jędrzejewska B. Design of dyes based on the quinoline or quinoxaline skeleton towards visible light photoinitiators. Int. J. Mol. Sci. 2024 25 8 4289 10.3390/ijms25084289 38673872
    [Google Scholar]
  9. Ahammed K.S. Pal R. Chakraborty J. Kanungo A. Purnima P.S. Dutta S. DNA structural alteration leading to antibacterial properties of 6-nitroquinoxaline derivatives. J. Med. Chem. 2019 62 17 7840 7856 10.1021/acs.jmedchem.9b00599 31390524
    [Google Scholar]
  10. Ren Z. Cui T. Zeng J. Chen L. Zhang W. Xu X. Cheng L. Li M. Li J. Zhou X. Li Y. Molecule targeting glucosyltransferase inhibits streptococcus mutans biofilm formation and virulence. Antimicrob. Agents Chemother. 2016 60 1 126 135 10.1128/AAC.00919‑15 26482298
    [Google Scholar]
  11. Kumar J. Chawla G. Kumar U. Sahu K. Design and syntheses of some new quinoxaline derivatives containing pyrazoline residue as potential antimicrobial agents. Med. Chem. Res. 2014 23 9 3929 3940 10.1007/s00044‑014‑0976‑2
    [Google Scholar]
  12. Cheng G. Li B. Wang C. Zhang H. Liang G. Weng Z. Hao H. Wang X. Liu Z. Dai M. Wang Y. Yuan Z. Systematic and molecular basis of the antibacterial action of quinoxaline 1,4-di-N-oxides against Escherichia coli. PLoS One 2015 10 8 0136450 10.1371/journal.pone.0136450 26296207
    [Google Scholar]
  13. El-Atawy M.A. Hamed E.A. Alhadi M. Omar A.Z. Synthesis and antimicrobial activity of some new substituted quinoxalines. Molecules 2019 24 22 4198 10.3390/molecules24224198 31752396
    [Google Scholar]
  14. Alfadil A. Ibrahem K.A. Alrabia M.W. Mokhtar J.A. Ahmed H. The fungicidal effectiveness of 2-chloro-3-hydrazinylquinoxaline against Candida species. PLoS One 2024 19 5 0303373 10.1371/journal.pone.0303373 38728271
    [Google Scholar]
  15. Ishikawa H. Sugiyama T. Yokoyama A. Synthesis of 2,3-bis(halomethyl)quinoxaline derivatives and evaluation of their antibacterial and antifungal activities. Chem. Pharm. Bull. 2013 61 4 438 444 10.1248/cpb.c12‑01061 23546003
    [Google Scholar]
  16. Rana M. Faizan M.I. Dar S.H. Ahmad T. Rahisuddin, Design and synthesis of carbothioamide/carboxamide-based pyrazoline analogs as potential anticancer agents: Apoptosis, molecular docking, ADME assay, and DNA Binding studies. ACS Omega 2022 7 26 22639 22656 10.1021/acsomega.2c02033 35811873
    [Google Scholar]
  17. Machado V. Cenci A.R. Teixeira K.F. Sens L. Tizziani T. Nunes R.J. Ferreira L.L.G. Yunes R.A. Sandjo L.P. Andricopulo A.D. de Oliveira A.S. Pyrazolines as potential anti-Alzheimer’s agents: DFT, molecular docking, enzyme inhibition and pharmacokinetic studies. RSC. Med. Chem. 2022 13 12 1644 1656 10.1039/D2MD00262K 36561075
    [Google Scholar]
  18. Aly M. An insight into the therapeutic impact of quinoxaline derivatives: Recent advances in biological activities (2020–2024). Results Chem. 2025 13 101989 10.1016/j.rechem.2024.101989
    [Google Scholar]
  19. Elfadil A. Alzahrani A.M. Abdullah H. Alsamhan H. Abujamel T.S. Ahmed H.E. Jiman-Fatani A. Evaluation of the antibacterial activity of quinoxaline derivative compound against methicillin-resistant Staphylococcus aureus. Infect. Drug Resist. 2023 16 2291 2296 10.2147/IDR.S401371 37095779
    [Google Scholar]
  20. Mokhtar J.A. Attallah D. Alquarni M.A. Ekhmimi T. Saleh B.H. Niyazi H.A. unveiling the efficacy of 3-hydrazinoquinoxaline-2-thiol against pseudomonas aeruginosa. Bahrain Med. Bull. 2025 47 1 15 20
    [Google Scholar]
  21. Ibrahem K. Alhazmi W. Niyazi H.A. Niyazi H.A. Saleh B. Ekhmimi T. Mokhtar J.A. Attallah D. Bazuhair M. Alkuwaity K. Sait A. Mufrrih M. Ismail M. Almoghrabi Y. Daghistani H. Alharbi O. Altayb H. Alfadil A. 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. 2024 18 4 2837 2849 10.22207/JPAM.18.4.55
    [Google Scholar]
  22. Burguete A. Pontiki E. Hadjipavlou-Litina D. Ancizu S. Villar R. Solano B. Moreno E. Torres E. Pérez S. Aldana I. Monge A. Synthesis and biological evaluation of new quinoxaline derivatives as antioxidant and anti-inflammatory agents. Chem. Biol. Drug Des. 2011 77 4 255 267 10.1111/j.1747‑0285.2011.01076.x 21244639
    [Google Scholar]
  23. Ahmed E.A. Mohamed M.F.A. Omran O.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 Advances 2022 12 39 25204 25216 10.1039/D2RA04498F 36199335
    [Google Scholar]
  24. Neri J.M. Siqueira P.E.A. Oliveira A.L.C.S.L. Araújo R.M. Araújo Júnior R.F. Martins A.A. Marques I.L. Silva R.A. Araújo A.A. Menezes F.G. Anticancer, anti-inflammatory and analgesic activities of aminoalcohol-based quinoxaline small molecules. Acta Cir. Bras. 2024 39 395124 10.1590/acb395124 39109780
    [Google Scholar]
  25. Pyszka I. Jędrzejewska B. Acenaphthoquinoxaline derivatives as dental photoinitiators of acrylates polymerization. Materials 2021 14 17 4881 10.3390/ma14174881 34500971
    [Google Scholar]
  26. Dumur F. Recent advances on quinoxaline-based photoini-tiators of polymerization. Catalysts 2023 13 4 718 10.3390/catal13040718
    [Google Scholar]
  27. Chen L. Chen W. Yu Y. Yang J. Jiang Q. Wu W. Yang D. 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. 2021 121 104625 10.1016/j.jmbbm.2021.104625 34130080
    [Google Scholar]
  28. Vitorino C. Sousa J. Pais A. Overcoming the oral cavity barriers to treat periodontal disease: Nanoparticles-based drug delivery systems. Int. J. Nanomedicine 2012 7 1469 1482
    [Google Scholar]
  29. Rezakhani L. Gharibshahian M. Salehi M. Zamani S. Abpeikar Z. Ghaderzadeh O. Alizadeh M. Masoudi A. Rezaei N. Cheraghali D. Recent advances in hydrogels applications for tissue engineering and clinical trials. Regen. Ther. 2024 26 635 645 10.1016/j.reth.2024.08.015 39281106
    [Google Scholar]
  30. Scalia S. Mezzena M. Incorporation of quercetin in lipid microparticles: Effect on photo- and chemical-stability. J. Pharm. Biomed. Anal. 2009 49 1 90 94 10.1016/j.jpba.2008.10.011 19042102
    [Google Scholar]
  31. Zhang Y. Jiang R. Lei L. Yang Y. Hu T. Drug delivery systems for oral disease applications. J. Appl. Oral Sci. 2022 30 20210349 10.1590/1678‑7757‑2021‑0349 35262595
    [Google Scholar]
  32. Kim Y. Zharkinbekov Z. Raziyeva K. Tabyldiyeva L. Berikova K. Zhumagul D. Temirkhanova K. Saparov A. Chitosan-based biomaterials for tissue regeneration. Pharmaceutics 2023 15 3 807 10.3390/pharmaceutics15030807 36986668
    [Google Scholar]
  33. Lu M. Ge Y. Qiu J. Shao D. Zhang Y. Bai J. Zheng X. Chang Z. Wang Z. Dong W. Tang C. Redox/pH dual-controlled release of chlorhexidine and silver ions from biodegradable mesoporous silica nanoparticles against oral biofilms. Int. J. Nanomedicine 2018 13 7697 7709 10.2147/IJN.S181168 30538453
    [Google Scholar]
  34. Huang C.Y. Huang T.H. Kao C.T. Wu Y.H. Chen W.C. Shie M.Y. Mesoporous calcium silicate nanoparticles with drug delivery and odontogenesis properties. J. Endod. 2017 43 1 69 76 10.1016/j.joen.2016.09.012 27939733
    [Google Scholar]
  35. Priyadarshini B.M. Mitali K. Lu T.B. Handral H.K. Dubey N. Fawzy A.S. PLGA nanoparticles as chlorhexidine-delivery carrier to resin-dentin adhesive interface. Dent. Mater. 2017 33 7 830 846 10.1016/j.dental.2017.04.015 28506608
    [Google Scholar]
  36. Hu F. Zhou Z. Xu Q. Fan C. Wang L. Ren H. Xu S. Ji Q. Chen X. A novel pH-responsive quaternary ammonium chitosan-liposome nanoparticles for periodontal treatment. Int. J. Biol. Macromol. 2019 129 1113 1119 10.1016/j.ijbiomac.2018.09.057 30218737
    [Google Scholar]
  37. Shrestha S. Kishen A. Temporal-controlled bioactive molecules releasing core-shell nano-system for tissue engineering strategies in endodontics. Nanomedicine 2019 18 11 20 10.1016/j.nano.2019.02.013 30844574
    [Google Scholar]
  38. Chen W. Zhi M. Feng Z. Gao P. Yuan Y. Zhang C. Wang Y. Dong A. Sustained co-delivery of ibuprofen and basic fibroblast growth factor by thermosensitive nanoparticle hydrogel as early local treatment of peri-implantitis. Int. J. Nanomedicine 2019 14 1347 1358 10.2147/IJN.S190781 30863065
    [Google Scholar]
  39. Tan J. Zhang M. Hai Z. Wu C. Lin J. Kuang W. Tang H. Huang Y. Chen X. Liang G. Sustained release of two bioactive factors from supramolecular hydrogel promotes periodontal bone regeneration. ACS Nano 2019 13 5 5616 5622 10.1021/acsnano.9b00788 31059238
    [Google Scholar]
  40. Pan J. Deng J. Luo Y. Yu L. Zhang W. Han X. You Z. Liu Y. Thermosensitive hydrogel delivery of human periodontal stem cells overexpressing platelet-derived growth factor-bb enhances alveolar bone defect repair. Stem Cells Dev. 2019 28 24 1620 1631 10.1089/scd.2019.0184 31663419
    [Google Scholar]
  41. He X.T. Li X. Xia Y. Yin Y. Wu R.X. Sun H.H. Chen F.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 Biomataer. 2019 88 162 180 10.1016/j.actbio.2019.02.004 30735811
    [Google Scholar]
  42. Silva C.R. Babo P.S. Gulino M. Costa L. Oliveira J.M. Silva-Correia J. Domingues R.M.A. Reis R.L. Gomes M.E. Injectable and tunable hyaluronic acid hydrogels releasing chemotactic and angiogenic growth factors for endodontic regeneration. Acta Biomater. 2018 77 155 171 10.1016/j.actbio.2018.07.035 30031163
    [Google Scholar]
  43. Yadlapati M. Biguetti C. Cavalla F. Nieves F. Bessey C. Bohluli P. Garlet G.P. Letra A. Fakhouri W.D. Silva R.M. Characterization of a vascular endothelial growth factor-loaded bioresorbable delivery system for pulp regeneration. J. Endod. 2017 43 1 77 83 10.1016/j.joen.2016.09.022 27939739
    [Google Scholar]
/content/journals/mrmc/10.2174/0113895575415392250904071753
Loading
Quinoxalines in Oral Health: From Antimicrobials to Biomaterials
Bentham Science Publishers ; https://doi.org/10.2174/0113895575415392250904071753
/content/journals/mrmc/10.2174/0113895575415392250904071753
/content/journals/mrmc/10.2174/0113895575415392250904071753
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: biomaterial ; Quinoxaline ; anti-inflammatory ; antimicrobial ; oral health ; quinoxalines

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