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2000
Volume 21, Issue 8
  • ISSN: 1573-4064
  • E-ISSN: 1875-6638

Abstract

The emergence of multidrug-resistant microbial strains poses a significant challenge to global public health. In response, researchers have been exploring innovative antimicrobial agents with enhanced efficacy and novel mechanisms of action. One promising approach involves the synthesis of hybrid molecules combining azetidinone and azole moieties, capitalizing on the respective antimicrobial properties of both structural elements. Natural and synthetic azetidinone derivatives hold a prominent position among medicinally significant compounds due to their varied and potent antibiotic activities. Interest persists in discovering new synthetic methods and refining existing ones, as well as applying these methods to create novel, biologically active azetidinone derivatives. Additionally, azoles are highly regarded in pharmaceuticals for their broad efficacy, tolerability, and oral availability. By merging these two pharmacophores, researchers aim to create compounds with synergistic or additive antimicrobial effects, potentially overcoming existing resistance mechanisms. Various synthetic strategies, including click chemistry and multicomponent reactions, have been employed to prepare these hybrid molecules efficiently. The antimicrobial potential of azetidinone-azole conjugates has been extensively evaluated against a spectrum of pathogens, including bacteria, fungi, and protozoa. These studies have demonstrated promising results, with several compounds exhibiting potent activity against both Gram-positive and Gram-negative bacteria, as well as clinically relevant fungal strains. Furthermore, SAR studies have provided valuable insights into the key structural features governing the antimicrobial properties of these conjugates, facilitating further optimization and rational design. In conclusion, the development of azetidinone-azole hybrids represents a promising avenue in the quest for novel antimicrobial agents. This study presents a comprehensive overview of recent advancements in synthesis and antimicrobial evaluation of azetidinone-azole conjugates.

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2025-12-05

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References

  1. DasR. Shilakari AsthanaG. SuriK.A. MehtaD.K. AsthanaA. Synthesis and assessment of antitubercular and antimicrobial activity of some novel triazolo and tetrazolo-fused 1, 3, 4-oxadiazole molecules containing pyrazine moiety.J. Pharm. Sci. Res.201573547
     [Google Scholar]
  2. LivermoreD.M. Bacterial resistance: Origins, epidemiology, and impact.Clin. Infect. Dis.200336Suppl. 1S11S2310.1086/34465412516026
     [Google Scholar]
  3. GouldK. Antibiotics: From prehistory to the present day.J. Antimicrob. Chemother.201671357257510.1093/jac/dkv48426851273
     [Google Scholar]
  4. ClardyJ. FischbachM.A. CurrieC.R. The natural history of antibiotics.Curr. Biol.20091911R437R44110.1016/j.cub.2009.04.00119515346
     [Google Scholar]
  5. Von DöhrenH. Antibiotics: Actions, origins, resistance, by C. Walsh. 2003. Washington, DC: ASM Press. 345 pp. $99.95 (hardcover).Protein Sci.200413113059306010.1110/ps.041032204
     [Google Scholar]
  6. DasR. MehtaD.K. DhanawatM. Exploring azatidinone moiety: An insight into its anti-tubercular potency.Drug Res.202171735536210.1055/a‑1481‑787934034345
     [Google Scholar]
  7. SamadhiyaP. SharmaR. SrivastavaS.K. SrivastavaS.D. Synthesis of 2-azetidinone derivatives of 6-nitro-1H-indazole and their biological importance.Quim. Nova201235591491910.1590/S0100‑40422012000500010
     [Google Scholar]
  8. MehtaP.D. SengarN.P.S. PathakA.K. 2-Azetidinone - A new profile of various pharmacological activities.Eur. J. Med. Chem.201045125541556010.1016/j.ejmech.2010.09.03520970895
     [Google Scholar]
  9. KumarA. RajputC.S. BhatiS.K. Synthesis of 3-[4′-(p-chlorophenyl)-thiazol-2′-yl]-2-[(substituted azetidinone/ thiazolidinone)-aminomethyl]-6-bromoquinazolin-4-ones as anti-inflammatory agent.Bioorg. Med. Chem.20071583089309610.1016/j.bmc.2007.01.04217317192
     [Google Scholar]
  10. SmithE.M. SorotaS. KimH.M. McKittrickB.A. NechutaT.L. BennettC. KnutsonC. BurnettD.A. KieselgofJ. TanZ. RindgenD. BridalT. ZhouX. JiaY.P. DongZ. MullinsD. ZhangX. PriestleyT. CorrellC.C. TulshianD. CzarnieckiM. GreenleeW.J. T-type calcium channel blockers: Spiro-piperidine azetidines and azetidinones—optimization, design and synthesis.Bioorg. Med. Chem. Lett.201020154602460610.1016/j.bmcl.2010.06.01220580233
     [Google Scholar]
  11. MehtaD.K. TayaP. DasR. DuaK. Design, synthesis and molecular docking studies of novel thiadiazole analogues with potential antimicrobial and antiinflammatory activities.Antiinflamm. Antiallergy Agents Med. Chem.20191829110910.2174/187152061966619030716244230848217
     [Google Scholar]
  12. DasR. AsthanaG.S. SuriK.A. MehtaD. AsthanaA. Recent developments in azole compounds as antitubercular agent.Mini Rev. Org. Chem.201916329030610.2174/1570193X15666180622144414
     [Google Scholar]
  13. TayaP. Kumar MehtaD. DasR. Design, synthesis, docking study and pharmacological evaluation of novel-2-(5-(1h-indol-3-yl)-1, 3, 4-thiadiazol-2-ylimino)-5-(substituted benzylidene) thiazolidine-4-one analogues.Int. J. Pharm. Sci. Res.201910701
     [Google Scholar]
  14. KanwarS. MehtaD.K. DasR. Greener approach as a recent advancement in the synthesis of thiadiazole.Int. J. Pharm. Sci. Rev. Res.201533140147
     [Google Scholar]
  15. DasR. MehtaD.K. GuptaS. DhanawatM. Design, synthesis, anti-microbial and molecular docking studies of novel 5-pyrazyl-2-sulfanyl-1, 3, 4-oxadiazole derivatives.Recent Adv. Antiinfect. Drug Discov.202217211813010.2174/277243441766622060910575535692159
     [Google Scholar]
  16. BodeyG.P. Azole antifungal agents.Clin. Infect. Dis.199214Suppl. 1S161S16910.1093/clinids/14.Supplement_1.S1611314105
     [Google Scholar]
  17. BarryA.L. BrownS.D. In vitro studies of two triazole antifungal agents (voriconazole [UK-109,496] and fluconazole) against Candida species.Antimicrob. Agents Chemother.19964081948194910.1128/AAC.40.8.19488843312
     [Google Scholar]
  18. ClemonsK.V. HansonL.H. StevensD.A. Activities of the triazole D0870 in vitro and against murine blastomycosis.Antimicrob. Agents Chemother.19933751177117910.1128/AAC.37.5.11778517710
     [Google Scholar]
  19. ClemonsK.V. StevensD.A. Efficacies of two novel azole derivatives each containing a morpholine ring, UR-9746 and UR-9751, against systemic murine coccidioidomycosis.Antimicrob. Agents Chemother.199741120020310.1128/AAC.41.1.2008980782
     [Google Scholar]
  20. DasR. MehtaD.K. Evaluation and docking study of pyrazine containing 1, 3, 4-oxadiazoles clubbed with substituted azetidin-2-one: A new class of potential antimicrobial and antitubercular.Drug Res.2021711263510.1055/a‑1252‑237833027823
     [Google Scholar]
  21. SainiM. DasR. MehtaD.K. Design, synthesis, and pharmacological evaluation of substituted oxadiazole-pyridazin-3-one derivatives as antioxidant and antimicrobial agents.Antiinfect. Agents2022204e17032220232510.2174/2211352520666220317142519
     [Google Scholar]
  22. SinghP. RajR. KumarV. MahajanM.P. BediP.M.S. KaurT. SaxenaA.K. 1,2,3-Triazole tethered β-lactam-Chalcone bifunctional hybrids: Synthesis and anticancer evaluation.Eur. J. Med. Chem.201247159460010.1016/j.ejmech.2011.10.03322071256
     [Google Scholar]
  23. DubeyA. SrivastavaS.K. SrivastavaS.D. Conventional and microwave assisted synthesis of 2-oxo-4-substituted aryl-azetidine derivatives of benzotriazole: A new class of biological compounds.Bioorg. Med. Chem. Lett.201121156957310.1016/j.bmcl.2010.10.05721130647
     [Google Scholar]
  24. VatmurgeN.S. HazraB.G. PoreV.S. ShiraziF. ChavanP.S. DeshpandeM.V. Synthesis and antimicrobial activity of β-lactam-bile acid conjugates linked via triazole.Bioorg. Med. Chem. Lett.20081862043204710.1016/j.bmcl.2008.01.10218267360
     [Google Scholar]
  25. VatmurgeN.S. HazraB.G. PoreV.S. ShiraziF. DeshpandeM.V. KadreppaS. ChattopadhyayS. GonnadeR.G. Synthesis and biological evaluation of bile acid dimers linked with 1,2,3-triazole and bis-β-lactam.Org. Biomol. Chem.20086203823383010.1039/b809221d18843413
     [Google Scholar]
  26. TajT. KambleR.R. GireeshT. BadamiB. An expeditious green synthesis of Schiff bases and azetidinones derivatised with 1,2,4-triazoles.J. Chem. Sci.2011123565766610.1007/s12039‑011‑0138‑8
     [Google Scholar]
  27. KhanT. YadavR. GoundS.S. An efficient synthesis and antibacterial activity of some novel 2‐azetidinone derivatives of 4h‐1,2,4‐triazoles under mild conditions.J. Heterocycl. Chem.20185541042104710.1002/jhet.3136
     [Google Scholar]
  28. DhallE. JainS. MishraA. DwivediJ. SharmaS. Synthesis and evaluation of some phenyl substituted azetidine containing 1, 2, 4‐triazole derivatives as antibacterial agents.J. Heterocycl. Chem.201855122859286910.1002/jhet.3357
     [Google Scholar]
  29. DhawanS. AwoladeP. KistenP. CeleN. PillayA.S. SahaS. KaurM. JonnalagaddaS.B. SinghP. Synthesis, cytotoxicity and antimicrobial evaluation of new coumarin‐tagged β ‐lactam triazole hybrid.Chem. Biodivers.2020171e190046210.1002/cbdv.20190046231788939
     [Google Scholar]
  30. SivaperumanA. NatarajanR. SubramaniA. AngamuthuP. Design, synthesis, docking, characterization and biological screening of novel azetidinone derivatives of nicotinic acid.Curr. Bioact. Compd.202118410421
     [Google Scholar]
  31. KaurR. SinghR. KumarA. KaurS. PriyadarshiN. SinghalN.K. SinghK. 1,2,3-Triazole β-lactam conjugates as antimicrobial agents.Heliyon202066e0424110.1016/j.heliyon.2020.e0424132637684
     [Google Scholar]
  32. PatelK.H. MehtaA.G. Synthesis of novel azetidinone and thiazolidinones derivatives and evaluation of their antimicrobial efficacy.E-J. Chem.20063103109
     [Google Scholar]
  33. CerićH. Šindler-KulykM. KovačevićM. PerićM. ŽivkovićA. Azetidinone-isothiazolidinones: Stereoselective synthesis and antibacterial evaluation of new monocyclic beta-lactams.Bioorg. Med. Chem.20101893053305810.1016/j.bmc.2010.03.04520382539
     [Google Scholar]
  34. SaundaneA.R. WalmikP. Synthesis, antioxidant, antimicrobial, antimycobacterial, and cytotoxic activities of azetidinone and thiazolidinone moieties linked to indole nucleus.J. Chem.20132013154381510.1155/2013/543815
     [Google Scholar]
  35. SankarP.S. DivyaK. ReddyG.D. PadmavathiV. ZyryanovG.V. Synthesis, characterization and antimicrobial activity of azetidinone and thiazolidinone derivatives.AIP Conference Proceedings,20192063133135510.1063/1.5087379
     [Google Scholar]
  36. ParikhK.A. OzaP.S. BhattS.B. ParikhA.R. A synthesis of some new 2-azetidinones as potential antitubercular agents.ChemInform200032126127210.1002/CHIN.200119111
     [Google Scholar]
  37. SamadhiyaP. SharmaR. SrivastavaS. SrivastavaS. Synthesis of 2-oxo-azetidine derivatives of 2-amino thiazole and their biological activity.J. Serb. Chem. Soc.201277559960510.2298/JSC110616002S
     [Google Scholar]
  38. DesaiN.C. HarsoraJ.P. MonaparaJ.D. KhedkarV.M. Synthesis, antimicrobial capability and molecular docking of heterocyclic scaffolds clubbed by 2-azetidinone, thiazole and quinoline derivatives.Polycycl. Aromat. Compd.20224273924393810.1080/10406638.2021.1877747
     [Google Scholar]
  39. SrivastavaS.K. SrivastavaS. SrivastavaS.D. Synthesis of new 1, 2, 4-triazolo-thiadiazoles and its 2-oxoazetidines as antimicrobial, anticonvulsant and antiinflammatory agents. Ind. J. Chem. - Sect. B Org.Med. Chem.20024123572363
     [Google Scholar]
  40. SonwaneS.K. SrivastavaS.D. SrivastavaS.K. Synthesis and antimicrobial activity of 2-(2′-arylidene-hydrazino-acetyl-amino)-4-phenyl-1,3-thiazoles and 2-[2′-{4″-substituted-aryl- 3″-chloro-2″-oxo-azetidine}-acetyl-amino]-4-phenyl-1,3-thiazoles. Ind. J. Chem. - Sect. B Org.Med. Chem.200847633636
     [Google Scholar]
  41. BabuN.M. BhushanB. MadhavanV. Synthesis and biological activity of some novel 1, 3, 4-thiadiazole derivatives.Int. J. Chemtech Res.20124234251
     [Google Scholar]
  42. PatelH. MishraL. NoolviM. KarpoormathR. CameotraS.S. Synthesis, in vitro evaluation, and molecular docking studies of azetidinones and thiazolidinones of 2-amino-5-cyclopropyl-1,3,4-thiadiazole as antibacterial agents.Arch. Pharm.2014347966868410.1002/ardp.20140014025066774
     [Google Scholar]
  43. GuruN. SrivastavaS.D. Synthesis of some new 1-[5′-{(2-benzothiazolylthio) methyl}-1′, 3′, 4′-thiadiazol-2′-yl]-4-substituted-3-chloro-2-azetidinones: Antimicrobial agent.J. Scient. Indus. Res.200160760160510.1016/j.jscs.2011.11.008
     [Google Scholar]
  44. KhanumS.A. ShashikanthS. SathyanarayanaS.G. LokeshS. DeepakS.A. Synthesis and antifungal activity of 2‐azetidinonyl‐5‐(2‐benzoylphenoxy)methyl‐1,3,4‐oxadiazoles against seed‐borne pathogens of Eleusine coracana (L.).Gaertn. Pest Manag. Sci.200965777678010.1002/ps.175219319825
     [Google Scholar]
  45. SreeramuluJ. AshokgajapathirajuP. Synthesis and antimicrobial activity of novel indol compounds containing 2-azitidinones and 1,3,4 oxadiazoles.Orient. J. Chem.201430265166010.13005/ojc/300234
     [Google Scholar]
  46. HeraviM.M. ZadsirjanV. Recent advances in biginelli-type reactions.Curr. Org. Chem.202024121331136610.2174/1385272824999200616111228
     [Google Scholar]
  47. YenireddyV.R. VejendlaA. Synthesis, characterization, biological evaluation and molecular docking of novel amide derivatives of indole-1,2,4-oxadiazole clubbed thiazoles.Chemical Data Collections20223910086110.1016/j.cdc.2022.100861
     [Google Scholar]
  48. Shafakat AliN. DarB. PradhanV. FarooquiM. Chemistry and biology of indoles and indazoles: A mini-review.Mini Rev. Med. Chem.201313121792180010.2174/138955751131312000922625410
     [Google Scholar]
  49. BhattJ.J. DhakhdaS.K. TrivediM.H. Synthesis, characterization and anti-microbial activity of pyrazole capped 2-azitidinone derivatives.Res. J. Life Sci. Bioinform. Pharm. Chem. Sci.20195647662
     [Google Scholar]
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Recent Developments in Azetidinone-Azole Conjugates: Emerging Antimicrobial Potentials
Med. Chem. 21, 761 (2025); https://doi.org/10.2174/0115734064355361241230063744
/content/journals/mc/10.2174/0115734064355361241230063744
/content/journals/mc/10.2174/0115734064355361241230063744
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  • Article Type:     Review Article
Keyword(s): antimicrobials; Azetidinone; azoles; tetrazoles; thiazoles; triazole

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