Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Medicinal Chemistry
  4. Fast Track Articles
  5. Fast Track Article
image of Recent Developments in Azetidinone-Azole Conjugates: Emerging Antimicrobial Potentials

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.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/mc/10.2174/0115734064355361241230063744
2025-01-08
2025-05-05

  • From This Site

    /content/journals/mc/10.2174/0115734064355361241230063744
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Das R. Shilakari Asthana G. Suri K.A. Mehta D.K. Asthana A. 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. 2015 7 35 47
    [Google Scholar]
  2. Livermore D.M. Bacterial resistance: Origins, epidemiology, and impact. Clin. Infect. Dis. 2003 36 Suppl. 1 S11 S23 10.1086/344654 12516026
    [Google Scholar]
  3. Gould K. Antibiotics: From prehistory to the present day. J. Antimicrob. Chemother. 2016 71 3 572 575 10.1093/jac/dkv484 26851273
    [Google Scholar]
  4. Clardy J. Fischbach M.A. Currie C.R. The natural history of antibiotics. Curr. Biol. 2009 19 11 R437 R441 10.1016/j.cub.2009.04.001 19515346
    [Google Scholar]
  5. Von Döhren H. Antibiotics: Actions, origins, resistance, by C. Walsh. 2003. Washington, DC: ASM Press. 345 pp. $99.95 (hardcover). Protein Sci. 2004 13 11 3059 3060 10.1110/ps.041032204
    [Google Scholar]
  6. Das R. Mehta D.K. Dhanawat M. Exploring azatidinone moiety: An insight into its anti-tubercular potency. Drug Res. 2021 71 7 355 362 10.1055/a‑1481‑7879 34034345
    [Google Scholar]
  7. Samadhiya P. Sharma R. Srivastava S.K. Srivastava S.D. Synthesis of 2-azetidinone derivatives of 6-nitro-1H-indazole and their biological importance. Quim. Nova 2012 35 5 914 919 10.1590/S0100‑40422012000500010
    [Google Scholar]
  8. Mehta P.D. Sengar N.P.S. Pathak A.K. 2-Azetidinone - A new profile of various pharmacological activities. Eur. J. Med. Chem. 2010 45 12 5541 5560 10.1016/j.ejmech.2010.09.035 20970895
    [Google Scholar]
  9. Kumar A. Rajput C.S. Bhati S.K. Synthesis of 3-[4′-(p-chlorophenyl)-thiazol-2′-yl]-2-[(substituted azet-idinone/thiazolidinone)-aminomethyl]-6-bromoquinazolin-4-ones as anti-inflammatory agent. Bioorg. Med. Chem. 2007 15 8 3089 3096 10.1016/j.bmc.2007.01.042 17317192
    [Google Scholar]
  10. Smith E.M. Sorota S. Kim H.M. McKittrick B.A. Nechuta T.L. Bennett C. Knutson C. Burnett D.A. Kie-selgof J. Tan Z. Rindgen D. Bridal T. Zhou X. Jia Y.P. Dong Z. Mullins D. Zhang X. Priestley T. Correll C.C. Tulshian D. Czarniecki M. Greenlee W.J. T-type calcium channel blockers: Spiro-piperidine azetidines and azet-idinones—optimization, design and synthesis. Bioorg. Med. Chem. Lett. 2010 20 15 4602 4606 10.1016/j.bmcl.2010.06.012 20580233
    [Google Scholar]
  11. Mehta D.K. Taya P. Das R. Dua K. Design, synthesis and molecular docking studies of novel thiadiazole analogues with potential antimicrobial and antiinflammatory activities. Anti-inflamm. Antiall. Agents Med. Chem. 2019 18 2 91 109 10.2174/1871520619666190307162442 30848217
    [Google Scholar]
  12. Das R. Asthana G.S. Suri K.A. Mehta D. Asthana A. Recent developments in azole compounds as antitubercular agent. Mini Rev. Org. Chem. 2019 16 3 290 306 10.2174/1570193X15666180622144414
    [Google Scholar]
  13. Taya P. Kumar Mehta D. Das R. Design, synthesis, dock-ing study and pharmacological evaluation of novel-2-(5-(1h-indol-3-yl)-1, 3, 4-thiadiazol-2-ylimino)-5-(substituted ben-zylidene) thiazolidine-4-one analogues. Int. J. Pharm. Sci. Res. 2019 10 701
    [Google Scholar]
  14. Kanwar S. Mehta D.K. Das R. Greener approach as a re-cent advancement in the synthesis of thiadiazole. Int. J. Pharm. Sci. Rev. Res. 2015 33 140 147
    [Google Scholar]
  15. Das R. Mehta D.K. Gupta S. Dhanawat M. Design, syn-thesis, anti-microbial and molecular docking studies of novel 5-pyrazyl-2-sulfanyl-1, 3, 4-oxadiazole derivatives. Rec. Adv. Antiinfect. Drug Discov. 2022 17 2 118 130 10.2174/2772434417666220609105755 35692159
    [Google Scholar]
  16. Bodey G.P. Azole antifungal agents. Clin. Infect. Dis. 1992 14 Suppl. 1 S161 S169 10.1093/clinids/14.Supplement_1.S161 1314105
    [Google Scholar]
  17. Barry A.L. Brown S.D. In vitro studies of two triazole anti-fungal agents (voriconazole [UK-109,496] and fluconazole) against Candida species. Antimicrob. Agents Chemother. 1996 40 8 1948 1949 10.1128/AAC.40.8.1948 8843312
    [Google Scholar]
  18. Clemons K.V. Hanson L.H. Stevens D.A. Activities of the triazole D0870 in vitro and against murine blastomycosis. Antimicrob. Agents Chemother. 1993 37 5 1177 1179 10.1128/AAC.37.5.1177 8517710
    [Google Scholar]
  19. Clemons K.V. Stevens D.A. Efficacies of two novel azole derivatives each containing a morpholine ring, UR-9746 and UR-9751, against systemic murine coccidioidomycosis. Antimicrob. Agents Chemother. 1997 41 1 200 203 10.1128/AAC.41.1.200 8980782
    [Google Scholar]
  20. Das R. Mehta D.K. Evaluation and docking study of pyra-zine containing 1, 3, 4-oxadiazoles clubbed with substituted azetidin-2-one: A new class of potential antimicrobial and an-titubercular. Drug Res. 2021 71 1 26 35 10.1055/a‑1252‑2378 33027823
    [Google Scholar]
  21. Saini M. Das R. Mehta D.K. Design, synthesis, and phar-macological evaluation of substituted oxadiazole-pyridazin-3-one derivatives as antioxidant and antimicrobial agents. Antiinfect. Agents 2022 20 4 e170322202325 10.2174/2211352520666220317142519
    [Google Scholar]
  22. Singh P. Raj R. Kumar V. Mahajan M.P. Bedi P.M.S. Kaur T. Saxena A.K. 1,2,3-Triazole tethered β-lactam-Chalcone bifunctional hybrids: Synthesis and anticancer eval-uation. Eur. J. Med. Chem. 2012 47 1 594 600 10.1016/j.ejmech.2011.10.033 22071256
    [Google Scholar]
  23. Dubey A. Srivastava S.K. Srivastava S.D. Conventional and microwave assisted synthesis of 2-oxo-4-substituted ar-yl-azetidine derivatives of benzotriazole: A new class of bio-logical compounds. Bioorg. Med. Chem. Lett. 2011 21 1 569 573 10.1016/j.bmcl.2010.10.057 21130647
    [Google Scholar]
  24. Vatmurge N.S. Hazra B.G. Pore V.S. Shirazi F. Chavan P.S. Deshpande M.V. Synthesis and antimicrobial activity of β-lactam-bile acid conjugates linked via triazole. Bioorg. Med. Chem. Lett. 2008 18 6 2043 2047 10.1016/j.bmcl.2008.01.102 18267360
    [Google Scholar]
  25. Vatmurge N.S. Hazra B.G. Pore V.S. Shirazi F. Desh-pande M.V. Kadreppa S. Chattopadhyay S. Gonnade R.G. Synthesis and biological evaluation of bile acid dimers linked with 1,2,3-triazole and bis-β-lactam. Org. Biomol. Chem. 2008 6 20 3823 3830 10.1039/b809221d 18843413
    [Google Scholar]
  26. Taj T. Kamble R.R. Gireesh T. Badami B. An expeditious green synthesis of Schiff bases and azetidinones derivatised with 1,2,4-triazoles. J. Chem. Sci. 2011 123 5 657 666 10.1007/s12039‑011‑0138‑8
    [Google Scholar]
  27. Khan T. Yadav R. Gound S.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. 2018 55 4 1042 1047 10.1002/jhet.3136
    [Google Scholar]
  28. Dhall E. Jain S. Mishra A. Dwivedi J. Sharma S. Synthe-sis and evaluation of some phenyl substituted azetidine con-taining 1, 2, 4‐triazole derivatives as antibacterial agents. J. Heterocycl. Chem. 2018 55 12 2859 2869 10.1002/jhet.3357
    [Google Scholar]
  29. Dhawan S. Awolade P. Kisten P. Cele N. Pillay A.S. Saha S. Kaur M. Jonnalagadda S.B. Singh P. Synthesis, cytotoxicity and antimicrobial evaluation of new coumarin‐tagged β ‐lactam triazole hybrid. Chem. Biodivers. 2020 17 1 e1900462 10.1002/cbdv.201900462 31788939
    [Google Scholar]
  30. Sivaperuman A. Natarajan R. Subramani A. Angamuthu P. Design, synthesis, docking, characterization and biological screening of novel azetidinone derivatives of nicotinic acid. Curr. Bioact. Compd. 2021 18 410 421
    [Google Scholar]
  31. Kaur R. Singh R. Kumar A. Kaur S. Priyadarshi N. Singhal N.K. Singh K. 1,2,3-Triazole β-lactam conjugates as antimicrobial agents. Heliyon 2020 6 6 e04241 10.1016/j.heliyon.2020.e04241 32637684
    [Google Scholar]
  32. Patel K.H. Mehta A.G. Synthesis of novel azetidinone and thiazolidinones derivatives and evaluation of their antimicro-bial efficacy. E-J. Chem. 2006 3 103 109
    [Google Scholar]
  33. Cerić H. Šindler-Kulyk M. Kovačević M. Perić M. Živ-ković A. Azetidinone-isothiazolidinones: Stereoselective syn-thesis and antibacterial evaluation of new monocyclic beta-lactams. Bioorg. Med. Chem. 2010 18 9 3053 3058 10.1016/j.bmc.2010.03.045 20382539
    [Google Scholar]
  34. Saundane A.R. Walmik P. Synthesis, antioxidant, antimi-crobial, antimycobacterial, and cytotoxic activities of azet-idinone and thiazolidinone moieties linked to indole nucleus. J. Chem. 2013 2013 1 543815 10.1155/2013/543815
    [Google Scholar]
  35. Sankar P.S. Divya K. Reddy G.D. Padmavathi V. Zyryanov G.V. Synthesis, characterization and antimicrobial activity of azetidinone and thiazolidinone derivatives. AIP Conference Proceedings 2019 2063 1 331 355 10.1063/1.5087379
    [Google Scholar]
  36. Parikh K.A. Oza P.S. Bhatt S.B. Parikh A.R. A synthesis of some new 2-azetidinones as potential antitubercular agents. ChemInform 2000 32 1 261 272 10.1002/CHIN.200119111
    [Google Scholar]
  37. Samadhiya P. Sharma R. Srivastava S. Srivastava S. Syn-thesis of 2-oxo-azetidine derivatives of 2-amino thiazole and their biological activity. J. Serb. Chem. Soc. 2012 77 5 599 605 10.2298/JSC110616002S
    [Google Scholar]
  38. Desai N.C. Harsora J.P. Monapara J.D. Khedkar V.M. Synthesis, antimicrobial capability and molecular docking of heterocyclic scaffolds clubbed by 2-azetidinone, thiazole and quinoline derivatives. Polycycl. Aromat. Compd. 2022 42 7 3924 3938 10.1080/10406638.2021.1877747
    [Google Scholar]
  39. Srivastava S.K. Srivastava S. Srivastava S.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. 2002 41 2357 2363
    [Google Scholar]
  40. Sonwane S.K. Srivastava S.D. Srivastava S.K. Synthesis and antimicrobial activity of 2-(2′-arylidene-hydrazino- ace-tyl-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. 2008 47 633 636
    [Google Scholar]
  41. Narayana Babu M. Bhushan B. Madhavan V. Synthesis and biological activity of some novel 1, 3, 4-thiadiazole de-rivatives. Int. J. Chemtech Res. 2012 4 234 251
    [Google Scholar]
  42. Patel H. Mishra L. Noolvi M. Karpoormath R. Singh Cameotra 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. 2014 347 9 668 684 10.1002/ardp.201400140 25066774
    [Google Scholar]
  43. Guru N. Srivastava S.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. 2001 60 7 601 605 10.1016/j.jscs.2011.11.008
    [Google Scholar]
  44. Khanum S.A. Shashikanth S. Sathyanarayana S.G. Lokesh S. Deepak S.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. 2009 65 7 776 780 10.1002/ps.1752 19319825
    [Google Scholar]
  45. Sreeramulu J. Ashokgajapathiraju P. Synthesis and antimi-crobial activity of novel indol compounds containing 2-azitidinones and 1,3,4 oxadiazoles. Orient. J. Chem. 2014 30 2 651 660 10.13005/ojc/300234
    [Google Scholar]
  46. Heravi M.M. Zadsirjan V. Recent advances in biginelli-type reactions. Curr. Org. Chem. 2020 24 12 1331 1366 10.2174/1385272824999200616111228
    [Google Scholar]
  47. Yenireddy V.R. Vejendla A. Synthesis, characterization, biological evaluation and molecular docking of novel amide derivatives of indole-1,2,4-oxadiazole clubbed thiazoles. Chemical Data Collections 2022 39 100861 10.1016/j.cdc.2022.100861
    [Google Scholar]
  48. Shafakat Ali N. Dar B. Pradhan V. Farooqui M. Chemis-try and biology of indoles and indazoles: A mini-review. Mini Rev. Med. Chem. 2013 13 12 1792 1800 10.2174/1389557511313120009 22625410
    [Google Scholar]
  49. Bhatt J.J. Dhakhda S.K. Trivedi M.H. Synthesis, character-ization and anti-microbial activity of pyrazole capped 2-azitidinone derivatives. Res. J. Life Sci. Bioinform. Pharm. Chem. Sci. 2019 5 647 662
    [Google Scholar]
/content/journals/mc/10.2174/0115734064355361241230063744
Loading
Recent Developments in Azetidinone-Azole Conjugates: Emerging Antimicrobial Potentials
Bentham Science Publishers ; https://doi.org/10.2174/0115734064355361241230063744
/content/journals/mc/10.2174/0115734064355361241230063744
/content/journals/mc/10.2174/0115734064355361241230063744
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: Azetidinone ; triazole ; azoles ; thiazoles ; antimicrobials ; tetrazoles

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