Skip to content
2000
image of Advance Screening of Bis- Azetidinone Derivatives: Synthesis, Spectroscopy, Antioxidant and Antimicrobial Analysis with Molecular Docking Assessment

Abstract

Introduction

This study includes synthesis, characterizations, antimicrobial, antioxidant, and docking molecular study of novel Bis-Azetidinone compounds that combined two units of β-lactam rings. In the present investigation, the aromatic aldehydes with primary amine were condensed to create Schiff's base, which was then reacted with chloroacetylchloride to produce bis-Azetidinone compounds.

Methods

Melting points, FTIR, and NMR spectrum analyses were used to examine the morphological and topological characteristics of the Bis-Azetidinone compounds. The results indicate that the prepared Compounds synthesis has excellent antimicrobial activity against both Gram-negative (,), Gram-positive bacteria () and fungal () and also indicated that the Compounds synthesis (A2) gave a higher antimicrobial effect than the B2, C2. The synergistic activity was examined against the pathogenic microbial strains. It was observed that employing compound synthesis combined with antibiotics enhanced the synergistic efficacy compared to using compound synthesis alone or antibiotic alone on Gram-positive bacteria and fungi.

Results

The antioxidant efficiency was assessed by DPPH, the results show that the compound synthesis has antioxidant activity, and also indicated that the synthesized compound (A2) gave a higher antioxidant effect than the B2, C2. Docking study confirmed redocking of crystalized substrate or inhibitor within target binding pocket. The docking results reveal that the synthesized compounds, with a total binding affinity of less than -48 kcal/mol, could be clinically used for future therapeutic purposes.

Conclusion

The present research demonstrates the advantageous effectiveness of a simpler production procedure, novel Bis-Azetidinone compounds, for producing high-purity with low hazard that may be utilized as future possible medical therapies.

Loading

Article metrics loading...

/content/journals/cos/10.2174/0115701794318870240923073910
2024-10-24
2025-03-01
Loading full text...

Full text loading...

References

  1. Butler M.S. Henderson I.R. Capon R.J. Blaskovich M.A.T. Antibiotics in the clinical pipeline as of December 2022. J. Antibiot. (Tokyo) 2023 76 8 431 473 10.1038/s41429‑023‑00629‑8 37291465
    [Google Scholar]
  2. Terreni M. Taccani M. Pregnolato M. New antibiotics for multidrug-resistant bacterial strains: Latest research developments and future perspectives. Molecules 2021 26 9 2671 10.3390/molecules26092671 34063264
    [Google Scholar]
  3. Sayed D.S.E. Abdelrehim E.S.M. Spectroscopic details on the molecular structure of pyrimidine‑2‑thiones heterocyclic compounds: Computational and antiviral activity against the main protease enzyme of SARS-CoV-2. BMC Chem. 2022 16 1 82 10.1186/s13065‑022‑00881‑3 36324115
    [Google Scholar]
  4. Abdelrehim E.S.M. El-Sayed D.S. Synthesis, screening as potential antitumor of new poly heterocyclic compounds based on pyrimidine-2-thiones. BMC Chem. 2022 16 1 16 10.1186/s13065‑022‑00810‑4 35313953
    [Google Scholar]
  5. Hoang T.P.N. Ghori M.U. Conway B.R. Topical antiseptic formulations for skin and soft tissue infections. Pharmaceutics 2021 13 4 558 10.3390/pharmaceutics13040558 33921124
    [Google Scholar]
  6. Al-azawi K.F. Ahmed Z.W. Ali E.H. Khadom A.A. Abrahim H.H. Rashid K.H. Synthesis and characterization of (E)-4-(((4-(5-mercapto-1, 3, 4-oxadiazol-2-yl) phenyl) amino) methyl)-2-methoxyphenol as a novel corrosion inhibitor for mild-steel in acidic medium. Results Chem. 2023 5 100975 100975 10.1016/j.rechem.2023.100975
    [Google Scholar]
  7. Martin J.F. Alvarez-Alvarez R. Liras P. Penicillin-Binding Proteins, β-Lactamases, and β-Lactamase Inhibitors in β-Lactam-Producing Actinobacteria: Self-Resistance Mechanisms. Int. J. Mol. Sci. 2022 23 10 5662 10.3390/ijms23105662 35628478
    [Google Scholar]
  8. Turner J. Muraoka A. Bedenbaugh M. Childress B. Pernot L. Wiencek M. Peterson Y.K. The chemical relationship among beta-lactam antibiotics and potential impacts on reactivity and decomposition. Front. Microbiol. 2022 13 807955 10.3389/fmicb.2022.807955 35401470
    [Google Scholar]
  9. El-Sayed D.S. Elbadawy H.A. Khalil T.E. Rational modulation of N and O binding in Fe(III) complex formation derived from hydroxychloroquine: Synthesis, spectroscopic, computational, and docking simulation with human thrombin plasma. J. Mol. Struct. 2022 1254 132268 132268 10.1016/j.molstruc.2021.132268
    [Google Scholar]
  10. Sauvage E. Terrak M. Glycosyltransferases and transpeptidases/penicillin-binding proteins: Valuable targets for new antibacterials. Antibiotics (Basel) 2016 5 1 12 10.3390/antibiotics5010012 27025527
    [Google Scholar]
  11. Parcheta M. Świsłocka R. Orzechowska S. Akimowicz M. Choińska R. Lewandowski W. Recent developments in effective antioxidants: The structure and antioxidant properties. Materials (Basel) 2021 14 8 1984 10.3390/ma14081984 33921014
    [Google Scholar]
  12. Forman H.J. Zhang H. Targeting oxidative stress in disease: Promise and limitations of antioxidant therapy. Nat. Rev. Drug Discov. 2021 20 9 689 709 10.1038/s41573‑021‑00233‑1 34194012
    [Google Scholar]
  13. Elhusseiny A.F. El-Dissouky A. Mautner F. Tawfik E.M. El-Sayed D.S. An insight into non-covalent interactions in binary, ternary and quaternary copper (II) complexes: Synthesis, X-ray structure, DFT calculations, antimicrobial activity and molecular docking studies. Inorg. Chim. Acta 2022 532 120748 10.1016/j.ica.2021.120748
    [Google Scholar]
  14. Munteanu I.G. Apetrei C. Analytical Methods Used in Determining Antioxidant Activity: A Review. Int. J. Mol. Sci. 2021 22 7 3380 10.3390/ijms22073380 33806141
    [Google Scholar]
  15. Ding Y. Li Z. Xu C. Qin W. Wu Q. Wang X. Cheng X. Li L. Huang W. Fluorogenic Probes/Inhibitors of β‐Lactamase and their Applications in Drug‐Resistant Bacteria. Angew. Chem. Int. Ed. 2021 60 1 24 40 10.1002/anie.202006635 32592283
    [Google Scholar]
  16. Firth A. Prathapan P. Broad-spectrum therapeutics: A new antimicrobial class. Curr. Res. Pharmacol. Drug Discov. 2021 2 100011 10.1016/j.crphar.2020.100011 34870144
    [Google Scholar]
  17. Hancock R.E.W. Nijnik A. Philpott D.J. Modulating immunity as a therapy for bacterial infections. Nat. Rev. Microbiol. 2012 10 4 243 254 10.1038/nrmicro2745 22421877
    [Google Scholar]
  18. Deshayes S. Coquerel A. Verdon R. Neurological Adverse Effects Attributable to β-Lactam Antibiotics: A Literature Review. Drug Saf. 2017 40 12 1171 1198 10.1007/s40264‑017‑0578‑2 28755095
    [Google Scholar]
  19. Vardakas K.Z. Kalimeris G.D. Triarides N.A. Falagas M.E. An update on adverse drug reactions related to β-lactam antibiotics. Expert Opin. Drug Saf. 2018 17 5 499 508 10.1080/14740338.2018.1462334 29633867
    [Google Scholar]
  20. Armstrong T. Fenn S.J. Hardie K.R. JMM Profile: Carbapenems: A broad-spectrum antibiotic. J. Med. Microbiol. 2021 70 12 001462 10.1099/jmm.0.001462 34889726
    [Google Scholar]
  21. Al-Azawi K. Synthesis, characterization and antioxidant studies of quinazolin derivatives. Orient. J. Chem. 2016 32 1 585 590 10.13005/ojc/320166
    [Google Scholar]
  22. Borazjani Nassim Jarrahpour Aliasghar Rad Javad Sharifi Design, synthesis and biological evaluation of some novel diastereoselective β-lactams bearing 2-mercaptobenzothiazole and benzoquinoline. Med. Chem. Res 2019 29 329 393 10.1007/s00044‑018‑02287‑0
    [Google Scholar]
  23. 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. 2019 17 1 e1900462 10.1002/cbdv.201900462 31788939
    [Google Scholar]
  24. Hrichi H. Elkanzi N.A.A. Bakr R.B. Novel Β-lactams and Thiazolidinone Derivatives from 1,4-dihydroquinoxaline Schiff’s Base: Synthesis, Antimicrobial Activity and Molecular Docking Studies. Chem. J. Moldova 2020 15 1 86 94 10.19261/cjm.2019.647
    [Google Scholar]
  25. Farhan M.M. Guma M.A. Rabeea M.A. Ahmad I. Patel H. Synthesizes, characterization, molecular docking and in vitro bioactivity study of new compounds containing triple beta lactam rings. J. Mol. Struct. 2022 1269 133781 133781 10.1016/j.molstruc.2022.133781
    [Google Scholar]
  26. Alborz M. Synthesis and biological evaluation of some novel diastereoselective benzothiazole β-lactam conjugates. Eur. J. Med. Chem. 2018 143 283 291 10.1016/j.ejmech.2017.11.053
    [Google Scholar]
  27. Mishra M.K. Singh V.N. Ahmad K. Sharma S. Synthesis and antimicrobial activities of some novel diastereoselective monocyclic cis-β-lactams using 2-ethoxy carbonyl DCPN as a carboxylic acid activator. Mol. Divers. 2021 25 4 2073 2087 10.1007/s11030‑020‑10099‑x 32405920
    [Google Scholar]
  28. El-Kanzi N.A.A. Khalafallah A.K. Younis M. Effect of Iodine on the Antimicrobial Activity of New Spiro and Isolated β-Lactam Thiazolidinone Derivatives. Phosphorus Sulfur Silicon Relat. Elem. 2007 182 5 1163 1181 10.1080/10426500601149929
    [Google Scholar]
  29. Jasim Z.I. Rashid K.H. AL-Azawi K.F. Khadom A.A. Synthesis of Schiff-Based Derivative as a Novel Corrosion Inhibitor for Mild Steel in 1 M HCl Solution: Optimization, Experimental, and Theoretical Investigations. J. Bio Tribocorros. 2023 9 3 54 10.1007/s40735‑023‑00774‑5
    [Google Scholar]
  30. Malebari A.M. Fayne D. Nathwani S.M. O’Connell F. Noorani S. Twamley B. O’Boyle N.M. O’Sullivan J. Zisterer D.M. Meegan M.J. β-Lactams with antiproliferative and antiapoptotic activity in breast and chemoresistant colon cancer cells. Eur. J. Med. Chem. 2020 189 112050 112050 10.1016/j.ejmech.2020.112050 31954879
    [Google Scholar]
  31. Alves A.J.S. Alves N.G. Caratão C.C. Esteves M.I.M. Fontinha D. Bártolo I. Soares M.I.L. Lopes S.M.M. Prudêncio M. Taveira N. Pinho e Melo T.M.V.D. Spiro-lactams as novel antimicrobial agents. Curr. Top. Med. Chem. 2020 20 2 140 152 10.2174/1568026619666191105110049 31702503
    [Google Scholar]
  32. Bush K. Bradford P.A. β-Lactams and β-Lactamase Inhibitors: An Overview. Cold Spring Harb. Perspect. Med. 2016 6 8 a025247 10.1101/cshperspect.a025247 27329032
    [Google Scholar]
  33. González-Bello C. Rodríguez D. Pernas M. Rodríguez Á. Colchón E. β-Lactamase inhibitors to restore the efficacy of antibiotics against superbugs. J. Med. Chem. 2020 63 5 1859 1881 10.1021/acs.jmedchem.9b01279 31663735
    [Google Scholar]
  34. Obayes H. Theoretical studies on electrophilic aromatic substitution reaction for 8-hydroxyquinoline. Orient. J. Chem. 2016 32 1 253 260 10.13005/ojc/320127
    [Google Scholar]
  35. Berber N. Arslan M. Vural F. Ergun A. Gençer N. Arslan O. Synthesis of new series of thiazol‐(2(3 H )‐ylideneamino)benzenesulfonamide derivatives as carbonic anhydrase inhibitors. J. Biochem. Mol. Toxicol. 2020 34 12 e22596 10.1002/jbt.22596 32762006
    [Google Scholar]
  36. Hussein N.N. Al-Azawi K. Sulaiman G.M. Albukhaty S. Al-Majeed R.M.A. Jabir M. Al-Dulimi A.G. Mohammed H.A. Akhtar N. Alawaji R. A Alshammari A.A. Khan R.A. Silver-cored Ziziphus spina-christi extract-loaded antimicrobial nanosuspension: Overcoming multidrug resistance. Nanomedicine (Lond.) 2023 18 25 1839 1854 10.2217/nnm‑2023‑0185 37982771
    [Google Scholar]
  37. Jawad K. H. Jamagh F. K. Sulaiman G. M. Hasoon B. A. Antibacterial and antibiofilm activities of amikacin-conjugated gold nanoparticles: A promising formulation for contact lens preservation. Inorg. Chem. Commun. 2024 162 112286 112286 10.1016/j.inoche.2024.112286
    [Google Scholar]
  38. Hasoon B.A. Jawad K.H. Mohammed I.S. Hussein N.N. Al-azawi K.F. Jabir M.S. Silver nanoparticles conjugated amoxicillin: A promising nano-suspension for overcoming multidrug resistance bacteria and preservation of endotracheal tube. Inorg. Chem. Commun. 2024 165 112456 112456 10.1016/j.inoche.2024.112456
    [Google Scholar]
  39. Farj A.S. Synthesis, characterization and antimicrobial activity of novel Mannich bases. AIP Conf. Proc. 2022 2437 1 020090 10.1063/5.0092314
    [Google Scholar]
  40. Radka C.D. Grace C.R. Hasdemir H.S. Li Y. Rodriguez C.C. Rodrigues P. Oldham M.L. Qayyum M.Z. Pitre A. MacCain W.J. Kalathur R.C. Tajkhorshid E. Rock C.O. The carboxy terminus causes interfacial assembly of oleate hydratase on a membrane bilayer. J. Biol. Chem. 2024 300 2 105627 105627 10.1016/j.jbc.2024.105627 38211817
    [Google Scholar]
  41. Khelfaoui H. Harkati D. Saleh B.A. Molecular Docking, Molecular Dynamics Simulations and Reactivity, Studies on Approved Drugs Library Targeting ACE2 and SARS-CoV-2 Binding with ACE2. J. Biomol. Struct. Dyn. 2020 2020 1 17 10.1080/07391102.2020.1803967 32752951
    [Google Scholar]
  42. Kitchen D.B. Decornez H. Furr J.R. Bajorath J. Docking and scoring in virtual screening for drug discovery: Methods and applications. Nat. Rev. Drug Discov. 2004 3 11 935 949 10.1038/nrd1549 15520816
    [Google Scholar]
  43. Khalil T.E. El-Dissouky A. Al-Wahaib D. Abrar N.M. El-Sayed D.S. Synthesis, characterization, antimicrobial activity, 3D‐QSAR, DFT, and molecular docking of some ciprofloxacin derivatives and their copper(II) complexes. Appl. Organomet. Chem. 2020 34 12 e5998 10.1002/aoc.5998
    [Google Scholar]
  44. Issa A.A. Kamel M.D. El-Sayed D.S. Depicted simulation model for removal of second-generation antipsychotic drugs adsorbed on Zn-MOF: Adsorption locator assessment. J. Mol. Model. 2024 30 4 106 10.1007/s00894‑024‑05896‑2 38491151
    [Google Scholar]
  45. Ibraheem H.H. Issa A.A. El-Sayed D.S. Structural behavior and surface layer modification of (E)-N′-((1H-indol-3-yl) methylene)-4-chlorobenzohydrazide: Spectroscopic, DFT, biomedical activity and molecular dynamic simulation against Candida Albicans receptor. J. Mol. Struct. 2024 1312 138484 138484 10.1016/j.molstruc.2024.138484
    [Google Scholar]
  46. Issa A.A. Ibraheem H.H. El-Sayed D.S. Computational innovation of in situ metallic elements with zirconia as a novel possible carrier for chemotherapeutic medication. J. Mol. Model. 2024 30 1 14 10.1007/s00894‑023‑05815‑x
    [Google Scholar]
  47. Mettai M. Daoud I. Mesli F. Kenouche S. Melkemi N. Kherachi R. Belkadi A. Molecular docking/dynamics simulations, MEP analysis, bioisosteric replacement and ADME/T prediction for identification of dual targets inhibitors of Parkinson’s disease with novel scaffold. In Silico Pharmacol. 2023 11 1 3 10.1007/s40203‑023‑00139‑3 36687301
    [Google Scholar]
/content/journals/cos/10.2174/0115701794318870240923073910
Loading
/content/journals/cos/10.2174/0115701794318870240923073910
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.


  • Article Type:
    Research Article
Keywords: docking study ; antioxidant ; spectroscopy ; Bis-azetidinone ; schiff base ; antimicrobial
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