Synthesis of New Azoquinolone: Evaluation of Structural, Spectral Properties, and Antimicrobial Activity

Year 2025, Volume: 12 Issue: 4, 197 - 206

Öznur Ölmez Nalcıoğlu , Mehtap Yakut , Ayşe Gül Caniklioğlu

https://doi.org/10.18596/jotcsa.1719222

Abstract

A new azo dye containing quinolone (QANB) was synthesized by the ring-opening of pyranoquinolone (PQ), which was obtained from N-ethyl aniline and diethyl malonate. Surprisingly, we determined that under strong base conditions, azo coupling occurred at the 8-position of the quinolone group rather than at the 3-position of the pyroquinolone ring. Structure of 3-[1-ethyl-4-hydroxy-8-(4-nitro-phenylazo)-2-oxo-1,2-dihydro-quinolin-3-yl]-3-hydroxy-acrylic acid (QANB) was elucidated by 1H NMR, 13C NMR, 13C NMR DEPT, 13C NMR APT, 2D NMR (1H-1H COSY and 1H-13C HMQC) and HRMS Analyses. Moreover, we investigated the antimicrobial activity of QANB on eight different bacteria and two different yeasts. The disc diffusion method and the minimum inhibitory concentration value determination (MIC) were used for antimicrobial activity. QANB demonstrated broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria. However, it has effectively shown activity against E. aerogenes, which causes pneumonia, sepsis, urinary tract infections, and wound infections. QANB also showed significant activity against C. albicans. The fact that QANB is much more effective against C. albicans than nystatin, which is widely used as an antifungal drug, supports the idea that this compound can be used as a potential antifungal drug.

Keywords

Quinolone , pyranoquinolone , azo dyes , actibacterial activity , antifungal activity , Candida Albicans

Thanks

The authors are grateful to Giresun University Central Research Laboratory (GRUMLAB) for technical support and Giresun University Biology Department for technical support during antimicrobial study.

References

• 1. Andersson MI, MacGowan AP. Development of the quinolones. J Antimicrob Chemother [Internet]. 2003 May 1;51(90001):1–11. Available from: <URL>.
• 2. Andriole VT. The quinolones: Past, present, and future. Clin Infect Dis [Internet]. 2005 Jul 15;41(Supplement_2):S113–9. Available from: <URL>.
• 3. Oliphant CM, Green GM. Quinolones: A comprehensive review. 2002;65(3):455–64. Available from: <URL>.
• 4. Liu X, Deng J, Xu Z, Lv ZS. Recent advances of 2-Quinolone-based derivatives as anti-tubercular agents. Anti-Infective Agents [Internet]. 2018 May 3;16(1):4–10. Available from: <URL>.
• 5. Fan YL, Cheng XW, Wu JB, Liu M, Zhang FZ, Xu Z, et al. Antiplasmodial and antimalarial activities of quinolone derivatives: An overview. Eur J Med Chem [Internet]. 2018 Feb;146:1–14. Available from: <URL>.
• 6. Wang R, Xu K, Shi W. Quinolone derivatives: Potential anti‐HIV agent—development and application. Arch Pharm (Weinheim) [Internet]. 2019 Sep 5;352(9):1900045. Available from: <URL>.
• 7. Gao F, Zhang X, Wang T, Xiao J. Quinolone hybrids and their anti-cancer activities: An overview. Eur J Med Chem [Internet]. 2019 Mar;165:59–79. Available from: <URL>.
• 8. Zhang B. Quinolone derivatives and their antifungal activities: An overview. Arch Pharm (Weinheim) [Internet]. 2019 May 25;352(5):1800382. Available from: <URL>.
• 9. Singh PK, Singh RL. Bio-removal of azo dyes: A review. Int J Appl Sci Biotechnol [Internet]. 2017 Jun 29;5(2):108–26. Available from: <URL>.
• 10. Khan MN, Parmar DK, Das D. Recent applications of azo dyes: A paradigm shift from medicinal chemistry to biomedical sciences. Mini-Reviews Med Chem [Internet]. 2021 Jun;21(9):1071–84. Available from: <URL>.
• 11. Arslan Ö, Aydıner B, Yalçın E, Babür B, Seferoğlu N, Seferoğlu Z. 8-Hydroxyquinoline based push-pull azo dye: Novel colorimetric chemosensor for anion detection. J Mol Struct [Internet]. 2017 Dec;1149:499–509. Available from: <URL>.
• 12. Ölmez Nalcıoğlu Ö, Kılıç E, Haspulat Taymaz B, Kamış H. Synthesis of new azobenzo[c]cinnolines and investigation of electronic spectra and spectroelectrochemical behaviours. Spectrochim Acta Part A Mol Biomol Spectrosc [Internet]. 2021 Dec;263:120175. Available from: <URL>.
• 13. Ali Y, Hamid SA, Rashid U. Biomedical applications of aromatic azo compounds. Mini-Reviews Med Chem [Internet]. 2018 Oct 12;18(18):1548–58. Available from: <URL>.
• 14. Şener N, Mohammed HJA, Yerlikaya S, Celik Altunoglu Y, Gür M, Baloglu MC, et al. Anticancer, antimicrobial, and DNA protection analysis of novel 2,4-dihydroxyquinoline dyes. Dye Pigment [Internet]. 2018 Oct;157:11–9. Available from: <URL>.
• 15. Mezgebe K, Mulugeta E. Synthesis and pharmacological activities of azo dye derivatives incorporating heterocyclic scaffolds: a review. RSC Adv [Internet]. 2022;12(40):25932–46. Available from: <URL>.
• 16. Kumari R, Sunil D, Ningthoujam RS, Kumar NA. Azodyes as markers for tumor hypoxia imaging and therapy: An up-to-date review. Chem Biol Interact [Internet]. 2019 Jul;307:91–104. Available from: <URL>.
• 17. Li X, Cheng J, Gong Y, Yang B, Hu Y. Mapping hydrogen sulfide in rats with a novel azo-based fluorescent probe. Biosens Bioelectron [Internet]. 2015 Mar;65:302–6. Available from: <URL>.
• 18. Pandey N. Bacterial pathogenesis. In: Microbes of Medical Importance [Internet]. Iterative International Publishers, Selfypage Developers Pvt Ltd; 2024. p. 3–28. Available from: <URL>.
• 19. Sati H, Carrara E, Savoldi A, Hansen P, Garlasco J, Campagnaro E, et al. The WHO bacterial priority pathogens list 2024: A prioritisation study to guide research, development, and public health strategies against antimicrobial resistance. Lancet Infect Dis [Internet]. 2025 Sep;25(9):1033–43. Available from: <URL>.
• 20. Tang K, Zhao H. Quinolone antibiotics: Resistance and therapy. Infect Drug Resist [Internet]. 2023 Feb;16:811–20. Available from: <URL>.
• 21. Pham TDM, Ziora ZM, Blaskovich MAT. Quinolone antibiotics. Medchemcomm [Internet]. 2019;10(10):1719–39. Available from: <URL>.
• 22. Naghavi M, Vollset SE, Ikuta KS, Swetschinski LR, Gray AP, Wool EE, et al. Global burden of bacterial antimicrobial resistance 1990–2021: A systematic analysis with forecasts to 2050. Lancet [Internet]. 2024 Sep;404(10459):1199–226. Available from: <URL>.
• 23. Li K, Guo J, Liang R, Wang X, Chen Q, Wang J, et al. A review on antifungal activity of plant essential oils. Phyther Res [Internet]. 2025 Aug 9;39(8):3736–61. Available from: <URL>.
• 24. Liao H, Liu M, Wang M, Zhang D, Hao Y, Xie F. Exploring the potential of s-Triazine derivatives as novel antifungal agents: A review. Pharmaceuticals [Internet]. 2025 May 7;18(5):690. Available from: <URL>.
• 25. WHO. WHO fungal priority pathogens list to guide research, development and public health action [Internet]. 2022. Available from: <URL>.
• 26. WHO. WHO issues its first-ever reports on tests and treatments for fungal infections [Internet]. 2025. Available from: <URL>.
• 27. Soliman HN, Yahia IS. Synthesis and technical analysis of 6-butyl-3-[(4-chlorophenyl)diazenyl]-4-hydroxy-2H-pyrano[3,2-c] quinoline-2,5(6H)-dione as a new organic semiconductor: Structural, optical and electronic properties. Dye Pigment [Internet]. 2020 May;176:108199. Available from: <URL>.
• 28. Saeed AM, AlNeyadi SS, Abdou IM. Anticancer activity of novel Schiff bases and azo dyes derived from 3-amino-4-hydroxy-2H-pyrano[3,2-c]quinoline-2,5(6H)-dione. Heterocycl Commun [Internet]. 2020 Dec 31;26(1):192–205. Available from: <URL>.
• 29. Soliman H, Yahia I. Structure, properties, and thermal behavior of chemically synthesized 3-((2,5 Difluorophenyl)diazenyl)-6-ethyl-4-hydrox-2H-pyrano[3,2-c]quinoline-2,5(6H)-dione as new brand organic materials: Antimicrobial activity. Egypt J Solids [Internet]. 2023 Aug 1;45(1):1–23. Available from: <URL>.
• 30. Yakut M, Yılmaz M, Pekel T, Erkan S, Katırcı R, Biçer E. Manganese(III) acetate‐based radical cyclization reactions for pyranocoumarin and pyranoquinoline compounds: Synthesis, DFT and molecular docking studies. ChemistrySelect [Internet]. 2022 Nov 25;7(44):e202202787. Available from: <URL>.
• 31. Aly AA, Nieger M, Bräse S, Bakheet MEM. X-ray structure analyses of 4-Hydroxy-1-Methylquinolin-2(1H)-One, 6-Ethyl-4-Hydroxy-2 H-Pyrano[3,2-c]Quinoline-2,5(6H)-Dione, (E)-4-(2-Benzylidene-Hydrazineyl)Quinolin-2(1H)-One and Diethyl (E)-2-(2-(1-Methyl-2-Oxo-1,2-Dihydro-Quinolin-4-yl)Hydrazineylidene) Succinate. J Chem Crystallogr [Internet]. 2023 Mar 4;53(1):38–49. Available from: <URL>.
• 32. Murray PR, Baron EJ, Jorgensen JH, Landry ML, Pfaller MA. Manual of clinical microbiology [Internet]. Washington: ASM Press; 2007. Available from: <URL>.
• 33. Yiğit D, Yiğit N, Aktaş E, Özgen U. Ceviz (Juglans regia L.)’in antimikrobiyal aktivitesi. Türk Mikrobiyoloji Cemiy Derg [Internet]. 2009;39(1–2):7–11. Available from: <URL>.
• 34. Ibrahim MA, Hassanin HM, Gabr YAA, Alnamer YAS. Novel heterocyclic derivatives of pyrano[3,2-c]quinolinone from 3-(1-ethy1-4-hydroxy-2-oxo-2(1H)-quinolin-3-yl)-3-oxopropanoic acid. Eur J Chem [Internet]. 2010 Sep 30;1(3):195–9. Available from: <URL>.
• 35. Ismail MM, Othman ES, Mohammed HM. Synthesis and cyclization reactions with quinolinyl keto esters. I. chemical reactivity of quinolinyl beta-keto ester and quinolinyl alpha,beta-unsaturated ketones. Chem Pap [Internet]. 2005;59:117–26. Available from: <URL>.
• 36. Abass M, Othman ES. Chemistry of substituted quinolinones. III. synthesis and reactions of some novel 3-pyrazolyl-2-quinolinones. Synth Commun [Internet]. 2001 Jan 20;31(21):3361–76. Available from: <URL>.
• 37. Socrates G. Infrared and raman characteristic group frequencies: Tables and charts [Internet]. John Wiley & Sons; 2001. 1 p. Available from: <URL>.
• 38. Mirsadeghi FA, Rufchahi EM, Zarrabi S. Spectral characterization and computational studies of some new synthesized 3-arylazo-4-hydroxybenzo[h]quinolin-2(1H)-one dyes. J Mol Struct [Internet]. 2022 Nov;1268:133726. Available from: <URL>.
• 39. Hasani M, Nordstierna L, Martinelli A. Molecular dynamics involving proton exchange of a protic ionic liquid–water mixture studied by NMR spectroscopy. Phys Chem Chem Phys [Internet]. 2019;21(39):22014–21. Available from: <URL>.
• 40. Andrews JM. Determination of minimum inhibitory concentrations. J Antimicrob Chemother [Internet]. 2001 Jul 1;48(suppl_1):5–16. Available from: <URL>.
• 41. Sati SC, Khulbe K, Joshi S. Antibacterial evaluation of the himalayan medicinal plant Valeriana wallichii DC. (Valerianaceae). Res J Microbiol [Internet]. 2011;6(3):289–96. Available from: <URL>.
• 42. Webber M, Piddock LJV. Quinolone resistance in Escherichia coli. Vet Res [Internet]. 2001 May;32(3/4):275–84. Available from: <URL>.
• 43. Ruiz J. Mechanisms of resistance to quinolones: target alterations, decreased accumulation and DNA gyrase protection. J Antimicrob Chemother [Internet]. 2003 May 1;51(5):1109–17. Available from: <URL>.
• 44. Turan-Zitouni G, Altıntop MD, Özdemir A, Demirci F, Mohsen UA, Kaplancikli ZA. Yeni naftiridin hidrazon türevleri ve anti-mikrobiyal aktiviteleri. Cukurova Med J [Internet]. 2014 Jun 1;39(2):234–9. Available from: <URL>.
• 45. Mohammed HJA. 2, 4-dihidroksi kinolin türevi yeni diazo boyarmaddelerin sentezi ve antimikrobiyal özelliklerin incelenmesi. 2018.
• 46. Yahyazadeh A, Yousefi H. Synthesis, spectral features and biological activity of some novel hetarylazo dyes derived from 8-chloro-4-hydroxyl-2-quinolone. Spectrochim Acta Part A Mol Biomol Spectrosc [Internet]. 2014 Jan;117:696–701. Available from: <URL>.
• 47. Moradi Rufchahi EO, Pouramir H, Yazdanbakhsh MR, Yousefi H, Bagheri M, Rassa M. Novel azo dyes derived from 8-methyl-4-hydroxyl-2-quinolone: Synthesis, UV–vis studies and biological activity. Chinese Chem Lett [Internet]. 2013 May;24(5):425–8. Available from: <URL>.