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Dergiler / Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi / 2026 / Volume: 46 Issue: 2

Exploring the Antimicrobial Potential of 1,3,4-Oxadiazole Derivatives: Synthesis, Characterization, and Activity Against Clinically Significant Pathogens

İbrahim Pınar(VAN YUZUNCU YIL UNIVERSITY)0009-0003-7635-9829
Yamaç Tekintaş(IZMIR KATIP CELEBI UNIVERSITY)0000-0001-9437-7527
Burak Kuzu(VAN YÜZÜNCÜ YIL ÜNİVERSİTESİ)0000-0002-7305-7177
Sayfa
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Yayın Tarihi
2026-06-01
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⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

In summary, the synthesized 1,3,4-oxadiazole derivatives, particularly 11h and 11i, exhibited promising antimicrobial and antibiofilm activities, indicating their potential as core scaffolds for the design of new therapeutic agents targeting resistant bacterial strains.

📌 3 Maddede Bu Makale

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Amaç & Hipotez:The 1,3,4-oxadiazole ring is a structurally stable and pharmacologically active scaffold widely explored in drug discovery.
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Temel Bulgular & Veri:This study presents a practical synthetic approach for 2,5-diaryl-substituted 1,3,4-oxadiazole scaffolds and evaluates their antimicrobial and antibiofilm potential.
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Sonuç & Katkı:In summary, the synthesized 1,3,4-oxadiazole derivatives, particularly 11h and 11i, exhibited promising antimicrobial and antibiofilm activities, indicating their potential as core scaffolds for the design of new therapeutic agents targeting resistant bacterial strains.
🔬Tür:Research Article
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Antimicrobial design · Organohalogen · Oxadiazoles

Abstract

The 1,3,4-oxadiazole ring is a structurally stable and pharmacologically active scaffold widely explored in drug discovery. This study presents a practical synthetic approach for 2,5-diaryl-substituted 1,3,4-oxadiazole scaffolds and evaluates their antimicrobial and antibiofilm potential. A total of 14 novel compounds were synthesized and screened for antibacterial activity against four clinically relevant bacterial strains: Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 29212), Escherichia coli (NCTC 13846), and Salmonella enterica (RSKK 04059). Minimum inhibitory concentrations (MICs) were determined in micromolar (μM) ranges, and several compounds demonstrated promising antibacterial effects. Among them, compounds 11h and 11i were selected for further evaluation of antibiofilm activity. Both compounds significantly inhibited biofilm formation by S. aureus, E. faecalis, and S. enterica, even at concentrations below their MIC values. A dose-dependent inhibition profile was observed, indicating potential utility in targeting bacterial biofilms at low doses. Interestingly, no antibiofilm activity was observed against E. coli NCTC 13846; instead, biofilm formation appeared to increase at certain concentrations. In summary, the synthesized 1,3,4-oxadiazole derivatives, particularly 11h and 11i, exhibited promising antimicrobial and antibiofilm activities, indicating their potential as core scaffolds for the design of new therapeutic agents targeting resistant bacterial strains.

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Bu Makaleye Atıf Yap

Pınar, İ., Tekintaş, Y., Kuzu, B. (2026). Exploring the Antimicrobial Potential of 1,3,4-Oxadiazole Derivatives: Synthesis, Characterization, and Activity Against Clinically Significant Pathogens. Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi, Volume: 46 Issue: 2. https://doi.org/10.52794/hujpharm.1782013

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Kaynakça (40)

  1. Meanwell NA. Synopsis of some recent tactical application of bioisosteres in drug design. J Med Chem. 2011;54(8):2529–59. https://doi.org/10.1021/jm1013693
  2. Köprülü TK, Ökten S, Atalay VE, Tekin Ş, Çakmak O. Biological activity and molecular docking studies of some new quinolines as potent anticancer agents. Med Oncol. 2021;38(7):84. https://doi.org/10.1007/s12032-021-01530-w
  3. Gomtsyan A. Heterocycles in drugs and drug discovery. Chem Heterocycl Compd. 2012;48:7–10. https://doi.org/10.1007/s10593-012-0960-z
  4. de Miguel R, Montejano R, Stella-Ascariz N, Arribas JR. A safety evaluation of raltegravir for the treatment of HIV. Expert Opin Drug Saf. 2018;17(2):217–23. https://doi.org/10.1080/14740338.2018.1411903
  5. Dannenberg CA, Bizet V, Zou LH, Bolm C. Transition-Metal-Free Oxidative Iodination of 1,3,4-Oxadiazoles. Eur J Org Chem. 2015;2015(1):77–80. https://doi.org/10.1055/a-1707-0965
  6. Nelson JB, Fizazi K, Miller K, Higano C, Moul JW, Akaza H, et al. Phase 3, randomized, placebo-controlled study of zibotentan (ZD4054) in patients with castration-resistant prostate cancer metastatic to bone. Cancer. 2012;118(22):5709–18. https://doi.org/10.1038/pcan.2013.2
  7. Moroz AA, Dmitriev MV, Maslivets AN. Regioselective [3+2] cycloaddition of nitrile oxides to 1H-pyrrole-2,3-diones: synthesis of spiro[pyrroledioxazoles]. Chem Heterocycl Compd. 2021;57(12):1230–4. https://doi.org/10.1007/s10593-021-03047-6
  8. Elkaeed EB, Salam HA, Sabt A, Al-Ansary GH, Eldehna WM. Recent advancements in the development of anti-breast cancer synthetic small molecules. Molecules. 2021;26(24):7611. https://doi.org/10.3390/molecules26247611
  9. Banik BK, Sahoo BM, Kumar BVVR, Panda KC, Jena J, Mahapatra MK, et al. Green synthetic approach: An efficient eco-friendly tool for synthesis of biologically active oxadiazole derivatives. Molecules. 2021;26(4):1163. https://doi.org/10.3390/molecules26041163
  10. Ustabaş R, Süleymanoğlu N, Ünver Y, Direkel Ş. 5-(4-Bromobenzyl)-4-(4-(5-phenyl-1,3,4-oxadiazole-2-yl)phenyl)-2,4-dihydro-3H-1,2,4-triazole-3-one: Synthesis, characterization, DFT study and antimicrobial activity. J Mol Struct. 2020;1214:128217. https://doi.org/10.1016/j.molstruc.2020.128217
  11. Bankar GR, Nampurath GK, Nayak PG, Bhattacharya S. A possible correlation between the correction of endothelial dysfunction and normalization of high blood pressure levels by 1,3,4-oxadiazole derivative, an L-type Ca2+ channel blocker in deoxycorticosterone acetate and NG-nitro-l-arginine hypertensive rats. Chem Biol Interact. 2010;183(2):327–31. https://doi.org/10.1016/j.cbi.2009.11.001
  12. Rai KL, Linganna N. Synthesis and evaluation of antimitotic activity of alkylated 2-amino-1,3,4-oxadiazole derivatives. Il Farmaco. 2000;55(5):389–92. https://doi.org/10.1016/S0014-827X(00)00056-2
  13. Popov SA, Semenova MD, Baev DS, Sorokina IV, Zhukova NA, Frolova TS, et al. Lupane-type conjugates with amino acids, 1,3,4-oxadiazole and 1,2,5-oxadiazole-2-oxide derivatives: Synthesis, anti-inflammatory activity and in silico evaluation of target affinity. Steroids. 2019;150:108443. https://doi.org/10.1016/j.steroids.2019.108443
  14. El-Din MMG, El-Gamal MI, Abdel-Maksoud MS, Yoo KH, Oh CH. Synthesis and broad-spectrum antiproliferative activity of diarylamides and diarylureas possessing 1,3,4-oxadiazole derivatives. Bioorg Med Chem Lett. 2015;25(8):1692–9. https://doi.org/10.1016/j.bmcl.2015.03.001
  15. Ladani GG, Patel MP. Novel 1,3,4-oxadiazole motifs bearing a quinoline nucleus: synthesis, characterization and biological evaluation of their antimicrobial, antitubercular, antimalarial and cytotoxic activities. New J Chem. 2015;39(12):9848–57. https://doi.org/10.1039/C5NJ02566D
  16. Ningegowda R, Chandrashekharappa S, Singh V, Mohanlall V, Venugopala KN. Design, synthesis and characterization of novel 2-(2,3-dichlorophenyl)-5-aryl-1,3,4-oxadiazole derivatives for their anti-tubercular activity against Mycobacterium tuberculosis. Chem Data Collect. 2020;28:100431. https://doi.org/10.1016/j.cdc.2020.100431
  17. Liu HY, Prentice EL, Webber MA. Mechanisms of antimicrobial resistance in biofilms. NPJ Antimicrob Resist. 2024;2:27. https://doi.org/10.1038/s44259-024-00046-3
  18. Bhutani R, Pathak DP, Kapoor G, Husain A, Iqbal MA. Novel hybrids of benzothiazole-1,3,4-oxadiazole-4-thiazolidinone: Synthesis, in silico ADME study, molecular docking and in vivo anti-diabetic assessment. Bioorg Chem. 2019;83:6–19. https://doi.org/10.1016/j.bioorg.2018.10.025
  19. Kashaw SK, Gupta V, Kashaw V, Mishra P, Stables JP, Jain NK. Anticonvulsant and sedative-hypnotic activity of some novel 3-[5-(4-substituted) phenyl-1,3,4-oxadiazole-2yl]-2-styrylquinazoline-4(3H)-ones. Med Chem Res. 2010;19:250–61. https://doi.org/10.1007/s00044-009-9188-6
  20. De SS, Khambete MP, Degani MS. Oxadiazole scaffolds in anti-tuberculosis drug discovery. Bioorg Med Chem Lett. 2019;29(16):1999–2007. https://doi.org/10.1016/j.bmcl.2019.06.054
  21. Jagadeesh Prathap K, Himaja M, Mali SV, Munirajasekhar D. Synthesis of new (pyrazol-3-yl)-1,3,4-oxadiazole derivatives by unexpected aromatization during oxidative cyclization of 4,5-dihydro-1H-pyrazole-3-carbohydrazones and their biological activities. J Heterocycl Chem. 2014;51(3):726–32. https://doi.org/10.1002/jhet.1765
  22. Aminov R. History of antimicrobial drug discovery: Major classes and health impact. Biochem Pharmacol. 2017;133:4–19. https://doi.org/10.1016/j.bcp.2016.10.001
  23. Brown ED, Wright GD. Antibacterial drug discovery in the resistance era. Nature. 2016;529(7586):336–43. https://doi.org/10.1038/nature17042
  24. Desai NC, Bhatt N, Somani H, Trivedi A. Synthesis, antimicrobial and cytotoxic activities of some novel thiazole clubbed 1,3,4-oxadiazoles. Eur J Med Chem. 2013;67:54–9. https://doi.org/10.1016/j.ejmech.2013.06.029
  25. Shyma PC, Kalluraya B, Peethambar SK, Telkar S, Arulmoli T. Synthesis, characterization and molecular docking studies of some new 1,3,4-oxadiazolines bearing 6-methylpyridine moiety for antimicrobial property. Eur J Med Chem. 2013;68:394–404. https://doi.org/10.1016/j.ejmech.2013.07.019
  26. Khalilullah H, Khan S, Nomani MS, Ahmed B. Synthesis, characterization and antimicrobial activity of benzodioxane ring containing 1,3,4-oxadiazole derivatives. Arab J Chem. 2016;9:1029–1035. https://doi.org/10.1016/j.arabjc.2011.11.009
  27. Salahuddin, Mazumder A, Shaharyar M. Synthesis, antibacterial and anticancer evaluation of 5-substituted (1,3,4-oxadiazol-2-yl) quinoline. Med Chem Res. 2015;24:2514–28. https://doi.org/10.1007/s00044-014-1308-2
  28. Desai NC, Vaghani HV, Jethawa AM, Khedkar VM. In silico molecular docking studies of oxadiazole and pyrimidine bearing heterocyclic compounds as potential antimicrobial agents. Arch Pharm. 2021;354(10):2100134. https://doi.org/10.1002/ardp.202100134
  29. Desai NC, Wadekar KR, Mehta HK, Pandit UP, Khedkar VM. Design, synthesis, antibacterial activity and in silico studies of novel quinolone fused with triazine, thiadiazole and oxadiazole heterocycles. Polycycl Aromat Compd. 2023;43(1):154–66. https://doi.org/10.1080/10406638.2021.2009886
  30. Shi W, Qian X, Zhang R, Song G. Synthesis and quantitative structure–activity relationships of new 2,5-disubstituted-1,3,4-oxadiazoles. J Agric Food Chem. 2001;49(1):124–30. https://doi.org/10.1021/jf0007941
  31. Zheng X, Li Z, Wang Y, Chen W, Huang Q, Liu C, et al. Syntheses and insecticidal activities of novel 2,5-disubstituted 1,3,4-oxadiazoles. J Fluor Chem. 2003;123(2):163–9. https://doi.org/10.1016/S0022-1139(03)00168-4
  32. Bajaj S, Kumar MS, Tinwala H, Mayur YC. Design, synthesis, modelling studies and biological evaluation of 1,3,4-oxadiazole derivatives as potent anticancer agents targeting thymidine phosphorylase enzyme. Bioorg Chem. 2021;111:104873. https://doi.org/10.1016/j.bioorg.2021.104873
  33. Luo S, Xu X, Zhang P, Shi Q, Yang X, Li F. Autotandem catalyst: from acylhydrazones to N′,N′-methylaliphatic acylhydrazides via transfer hydrogenation/N-methylation with methanol catalyzed by a Cp* iridium complex bearing a functional ligand. Org Lett. 2022;24(49):9081–5. https://doi.org/10.1021/acs.orglett.2c03719
  34. Kuzu B, Yiğit A, Karakuş F. Design, synthesis, and evaluation of antibacterial potential of hydrazone-tethered pyrazole-thiazole derivatives. J Fac Pharm Ankara Univ. 2025;49(1):42–52. https://doi.org/10.33483/jfpau.1529096
  35. Yu W, Huang G, Zhang Y, Liu H, Dong L, Yu X, et al. I2-mediated oxidative C–O bond formation for the synthesis of 1,3,4-oxadiazoles from aldehydes and hydrazides. J Org Chem. 2013;78(20):10337–43. https://doi.org/10.1021/jo401751h
  36. Ozturk I, Tekintas Y, Temel A, Ermertcan S, Kurutepe S, Hosgor Limoncu M. In vitro effects of antibiofilm agents and antibiotics on coagulase-negative staphylococci. J Res Pharm. 2020;24(6):821–32. https://doi.org/10.35333/jrp.2020.241
  37. Uzunbayir-Akel N, Tekintas Y, Yilmaz FF, Ozturk I, Okeer M, Aydemir SS, et al. Effects of disinfectants and ciprofloxacin on quorum sensing genes and biofilm of clinical Pseudomonas aeruginosa isolates. J Infect Public Health. 2020;13(12):1932–8. https://doi.org/10.1016/j.jiph.2020.10.002
  38. Kaur N, Dey P. Bacterial exopolysaccharides as emerging bioactive macromolecules: from fundamentals to applications. Res Microbiol. 2023;174(4):104024. https://doi.org/10.1016/j.resmic.2022.104024
  39. Matuschek E, Åhman J, Webster C, Kahlmeter G. Antimicrobial susceptibility testing of colistin—evaluation of seven commercial MIC products against standard broth microdilution for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter spp. Clin Microbiol Infect. 2018;24(8):865–70. https://doi.org/10.1016/j.cmi.2017.11.020
  40. Ilangumaran Ponmalar I, Swain J, Basu JK. Escherichia coli response to subinhibitory concentrations of colistin: insights from a study of membrane dynamics and morphology. Biomater Sci. 2022;10(10):2609–17. https://doi.org/10.1039/D2BM00037G