Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Medicinal Chemistry
  4. Volume 20, Issue 9
  5. Article
Volume 20, Issue 9
  • ISSN: 1573-4064
  • E-ISSN: 1875-6638

Abstract

Introduction

Drug resistance to existing antimicrobial drugs has become a serious threat to human health, which highlights the need to develop new antimicrobial agents.

Methods

In this study, a new set of 3-hydroxypyridine-4-one derivatives () was synthesized, and the antimicrobial effects of these derivatives were evaluated against a variety of microorganisms using the microdilution method. The antimicrobial evaluation indicated that compound , with an electron-donating group -OCH at the meta position of the phenyl ring, was the most active compound against and species with an MIC value of 32 µg/mL. Compound was more potent than ampicillin as a reference drug.

Results

The antifungal results showed that the studied derivatives had moderate effects (MIC = 128-512 µg/mL) against . and species. The molecular modeling studies revealed the possible mechanism and suitable interactions of these derivatives with the target protein.

Conclusion

The obtained biological results offer valuable insights into the design of more effective antimicrobial agents.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/mc/10.2174/0115734064307744240523112710
2024-06-04
2025-04-15

  • From This Site

    /content/journals/mc/10.2174/0115734064307744240523112710
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Van DuinD. PatersonD.L. Multidrug-resistant bacteria in the community: Trends and lessons learned.Clin. Infect. Dis.2016302377390
     [Google Scholar]
  2. JainP. SharmaS. KumarN. MisraN. Ni(II) and Cu(II) complexes of bidentate thiosemicarbazone ligand: Synthesis, structural, theoretical, biological studies and molecular modeling.Appl. Organomet. Chem.2020349e573610.1002/aoc.5736
     [Google Scholar]
  3. KumarR. SeemaK. SinghD.K. JainP. ManavN. GautamB. KumarS.N. Synthesis, antibacterial and antifungal activities of Schiff base rare earth metal complexes: A review of recent work.J. Coord. Chem.2023769-101065109310.1080/00958972.2023.2231608
     [Google Scholar]
  4. SadeghianS. Evaluation of antibacterial and anticandidal activities of some imidazole, benzimidazole and benztriazole derivatives.Trends Pharmacol. Sci.2022827584
     [Google Scholar]
  5. van DuinD. PatersonD.L. Multidrug-resistant bacteria in the community: An update.Infect. Dis. Clin. North Am.202034470972210.1016/j.idc.2020.08.002 33011046
     [Google Scholar]
  6. JerniganJ.A. HatfieldK.M. WolfordH. NelsonR.E. OlubajoB. ReddyS.C. McCarthyN. PaulP. McDonaldL.C. KallenA. FioreA. CraigM. BaggsJ. Multidrug-resistant bacterial infections in US hospitalized patients, 2012–2017.N. Engl. J. Med.2020382141309131910.1056/NEJMoa1914433 32242356
     [Google Scholar]
  7. SadeghianS. BekhradiF. MansouriF. RazmiR. MansouriS.G. PoustforooshA. KhabnadidehS. ZomorodianK. ZareshahrabadiZ. RezaeiZ. Imidazole derivatives as novel and potent antifungal agents: Synthesis, biological evaluation, molecular docking study, molecular dynamic simulation and ADME prediction.J. Mol. Struct.2024130213744710.1016/j.molstruc.2023.137447
     [Google Scholar]
  8. HoubenR.M.G.J. DoddP.J. The global burden of latent tuberculosis infection: A re-estimation using mathematical modelling.PLoS Med.20161310e100215210.1371/journal.pmed.1002152 27780211
     [Google Scholar]
  9. Funda TayN. BerkB. DuranM. Kayagilİ. YurttaşL. Biltekin KaleliS.N. YamaçM. KaradumanA.B. DemirayakŞ. Synthesis, antimicrobial activity and modeling studies of thiazoles bearing pyridyl and triazolyl scaffolds.Z. Naturforsch. C J. Biosci.2022779-1042944610.1515/znc‑2022‑0002 35472438
     [Google Scholar]
  10. LuoX. SongY. CaoZ. QinZ. DessieW. HeN. WangZ. TanY. Evaluation of the antimicrobial activities and mechanisms of synthetic antimicrobial peptide against food-borne pathogens.Food Biosci.20224910190310.1016/j.fbio.2022.101903
     [Google Scholar]
  11. PisteD.P.B. Novel synthesis and antimicrobial activities of thiazino-oxazine derivatives.Int. J. Pharm. Sci. Drug Res.201810420621210.25004/IJPSDR.2018.100401
     [Google Scholar]
  12. RagabA. FouadS.A. AliO.A.A. AhmedE.M. AliA.M. AskarA.A. AmmarY.A. Sulfaguanidine hybrid with some new pyridine-2-one derivatives: design, synthesis, and antimicrobial activity against multidrug-resistant bacteria as dual DNA gyrase and DHFR inhibitors.Antibiotics202110216210.3390/antibiotics10020162 33562582
     [Google Scholar]
  13. EissaS.I. FarragA.M. AbbasS.Y. El ShehryM.F. RagabA. FayedE.A. AmmarY.A. Novel structural hybrids of quinoline and thiazole moieties: Synthesis and evaluation of antibacterial and antifungal activities with molecular modeling studies.Bioorg. Chem.202111010480310.1016/j.bioorg.2021.104803 33761314
     [Google Scholar]
  14. XuZ. 1,2,3-Triazole-containing hybrids with potential antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA).Eur. J. Med. Chem.202020611268610.1016/j.ejmech.2020.112686 32795773
     [Google Scholar]
  15. SanganiC.B. MakawanaJ.A. ZhangX. TeraiyaS.B. LinL. ZhuH.L. Design, synthesis and molecular modeling of pyrazole–quinoline–pyridine hybrids as a new class of antimicrobial and anticancer agents.Eur. J. Med. Chem.20147654955710.1016/j.ejmech.2014.01.018 24607998
     [Google Scholar]
  16. CuiS.F. PengL.P. ZhangH.Z. RasheedS. Vijaya KumarK. ZhouC.H. Novel hybrids of metronidazole and quinolones: Synthesis, bioactive evaluation, cytotoxicity, preliminary antimicrobial mechanism and effect of metal ions on their transportation by human serum albumin.Eur. J. Med. Chem.20148631833410.1016/j.ejmech.2014.08.063 25173851
     [Google Scholar]
  17. JeyakkumarP. ZhangL. AvulaS.R. ZhouC.H. Design, synthesis and biological evaluation of berberine-benzimidazole hybrids as new type of potentially DNA-targeting antimicrobial agents.Eur. J. Med. Chem.201612220521510.1016/j.ejmech.2016.06.031 27371924
     [Google Scholar]
  18. KantR. KumarD. AgarwalD. GuptaR.D. TilakR. AwasthiS.K. AgarwalA. Synthesis of newer 1,2,3-triazole linked chalcone and flavone hybrid compounds and evaluation of their antimicrobial and cytotoxic activities.Eur. J. Med. Chem.2016113344910.1016/j.ejmech.2016.02.041 26922227
     [Google Scholar]
  19. GondruR. KanugalaS. RajS. Ganesh KumarC. PasupuletiM. BanothuJ. BavantulaR. 1,2,3-triazole-thiazole hybrids: Synthesis, in vitro antimicrobial activity and antibiofilm studies.Bioorg. Med. Chem. Lett.20213312774610.1016/j.bmcl.2020.127746 33333162
     [Google Scholar]
  20. BhagatK. BhagatJ. GuptaM.K. SinghJ.V. GulatiH.K. SinghA. KaurK. KaurG. SharmaS. RanaA. SinghH. SharmaS. Singh BediP.M. Design, synthesis, antimicrobial evaluation, and molecular modeling studies of novel indolinedione–coumarin molecular hybrids.ACS Omega2019458720873010.1021/acsomega.8b02481 31459961
     [Google Scholar]
  21. MarinescuM. Synthesis of antimicrobial benzimidazole–pyrazole compounds and their biological activities.Antibiotics2021108100210.3390/antibiotics10081002 34439052
     [Google Scholar]
  22. LalK. PooniaN. RaniP. KumarA. KumarA. Design, synthesis, antimicrobial evaluation and docking studies of urea-triazole-amide hybrids.J. Mol. Struct.2020121512823410.1016/j.molstruc.2020.128234
     [Google Scholar]
  23. ChavesS. PiemonteseL. HiremathadA. SantosM.A. Hydroxypyridinone derivatives: A fascinating class of chelators with therapeutic applications-an update.Curr. Med. Chem.20182519711210.2174/0929867324666170330092304 28359230
     [Google Scholar]
  24. DaiX.Y. ZhangM-X. WeiX-Y. HiderR.C. ZhouT. Novel multifunctional hydroxypyridinone derivatives as potential shrimp preservatives.Food Bioprocess Technol.2016971079108810.1007/s11947‑016‑1694‑1
     [Google Scholar]
  25. SinghL.R. ChenY.L. XieY.Y. XiaW. GongX.W. HiderR.C. ZhouT. Functionality study of chalcone-hydroxypyridinone hybrids as tyrosinase inhibitors and influence on anti-tyrosinase activity.J. Enzyme Inhib. Med. Chem.20203511562156710.1080/14756366.2020.1801669 32746652
     [Google Scholar]
  26. ShaoL.L. WangX.L. ChenK. DongX.W. KongL.M. ZhaoD.Y. HiderR.C. ZhouT. Novel hydroxypyridinone derivatives containing an oxime ether moiety: Synthesis, inhibition on mushroom tyrosinase and application in anti-browning of fresh-cut apples.Food Chem.201824217418110.1016/j.foodchem.2017.09.054 29037675
     [Google Scholar]
  27. HeM. FanM. PengZ. WangG. An overview of hydroxypyranone and hydroxypyridinone as privileged scaffolds for novel drug discovery.Eur. J. Med. Chem.202122111354610.1016/j.ejmech.2021.113546 34023737
     [Google Scholar]
  28. FassihiA. HasanzadehF. AttarA. SaghaieL. MohammadpourM. Synthesis and evaluation of antioxidant activity of some novel hydroxypyridinone derivatives: A DFT approach for explanation of their radical scavenging activity.Res. Pharm. Sci.202015651552810.4103/1735‑5362.301336 33828595
     [Google Scholar]
  29. DehkordiM.M. AsgarshamsiM.H. FassihiA. ZborowskiK.K. A comparative DFT study on the antioxidant activity of some novel 3‐hydroxypyridine‐4‐one derivatives.Chem. Biodivers.2022193e20210070310.1002/cbdv.202100703 34997823
     [Google Scholar]
  30. Sadeghi-AliabadiH. ZanjanchiM.A. SaghaieL. BorzoeiM. Evaluation of the cytotoxic effect of hydroxypyridinone derivatives on HCT116 and SW480 colon cancer cell lines.Pharm. Chem. J.201953538839110.1007/s11094‑019‑02010‑2
     [Google Scholar]
  31. FaidallahH.M. RostomS.A.F. KhanK.A. BasaifS.A. Synthesis and characterization of some hydroxypyridone derivatives and their evaluation as antimicrobial agents.J. Enzyme Inhib. Med. Chem.201328592693510.3109/14756366.2012.694880 22803670
     [Google Scholar]
  32. SantosM.A. ChavesS. 3-hydroxypyridinone derivatives as metal-sequestering agents for therapeutic use.Future Med. Chem.20157338341010.4155/fmc.14.162 25826364
     [Google Scholar]
  33. ZhouT. ChenK. KongL.M. LiuM.S. MaY.M. XieY.Y. HiderR.C. Synthesis, iron binding and antimicrobial properties of hexadentate 3-hydroxypyridinones-terminated dendrimers.Bioorg. Med. Chem. Lett.201828142504251210.1016/j.bmcl.2018.05.058 29886020
     [Google Scholar]
  34. ZhouY.J. LiuM.S. OsamahA.R. KongX.L. AlsamS. BattahS. XieY.Y. HiderR.C. ZhouT. Hexadentate 3-hydroxypyridin-4-ones with high iron(III) affinity: Design, synthesis and inhibition on methicillin resistant Staphylococcus aureus and Pseudomonas strains.Eur. J. Med. Chem.20159482110.1016/j.ejmech.2015.02.050 25747496
     [Google Scholar]
  35. HassaniB. ZareF. EmamiL. KhoshneviszadehM. FazelR. KaveN. SabetR. SadeghpourH. Synthesis of 3-hydroxypyridin-4-one derivatives bearing benzyl hydrazide substitutions towards anti-tyrosinase and free radical scavenging activities.RSC Advances20231346324333244310.1039/D3RA06490E 37942455
     [Google Scholar]
  36. SadeghianS. ZareF. GoshtasbiG. FassihiA. SaghaieL. ZareP. SabetR. Synthesis, antimicrobial evaluation, molecular docking, and ADME studies of some novel 3‐hydroxypyridine‐4‐one derivatives.ChemistrySelect2023844e20230240810.1002/slct.202302408
     [Google Scholar]
  37. SabetR. FassihiA. SaghaieL. Octanol-water partition coefficients determination and QSPR study of some 3-hydroxy pyridine-4-one derivatives.J. Pharm. Res. Int.201822411610.9734/JPRI/2018/41142
     [Google Scholar]
  38. MuthukumarR. KarnanM. ElangovanN. KarunanidhiM. SankarapandianV. VenkateswaranK. Synthesis, experimental antimicrobial activity, theoretical vibrational analysis, quantum chemical modeling and molecular docking studies of (E)-4-(benzylideneamino)benzenesulfonamide.J. Mol. Struct.2022126313318710.1016/j.molstruc.2022.133187
     [Google Scholar]
  39. ZareF. Structure-based virtual screening, molecular docking, molecular dynamics simulation and MM/PBSA calculations towards identification of steroidal and non-steroidal selective glucocorticoid receptor modulators.J. Biomol. Struct. Dyn.2023411676407650 36134594
     [Google Scholar]
  40. EswaramoorthyR. HailekirosH. KedirF. EndaleM. In silico molecular docking, DFT analysis and ADMET studies of carbazole alkaloid and coumarins from roots of clausena anisata: A potent inhibitor for quorum sensing.Adv. Appl. Bioinform. Chem.202114132410.2147/AABC.S290912 33584098
     [Google Scholar]
  41. DebP.K. Al-Shar’iN.A. VenugopalaK.N. PillayM. BorahP. In vitro anti-TB properties, in silico target validation, molecular docking and dynamics studies of substituted 1,2,4-oxadiazole analogues against Mycobacterium tuberculosis.J. Enzyme Inhib. Med. Chem.202136186988410.1080/14756366.2021.1900162 34060396
     [Google Scholar]
  42. El-DeanA.M.K. Abdel-MoneamM.E. Synthesis of pyrimidines, thienopyrimidines, and pyrazolopyrimidines.Phosphorus Sulfur Silicon Relat. Elem.2002177122745275110.1080/10426500214894
     [Google Scholar]
  43. EnoE.A. MbonuJ.I. LouisH. Patrick-IneziF.S. GberT.E. UnimukeT.O. OkonE.E.D. BenjaminI. OffiongO.E. Antimicrobial activities of 1-phenyl-3-methyl-4-trichloroacetyl-pyrazolone: Experimental, DFT studies, and molecular docking investigation.J. Indian Chem. Soc.202299710052410.1016/j.jics.2022.100524
     [Google Scholar]
  44. FanJ. FuA. ZhangL. Progress in molecular docking.Quant. Biol.201972838910.1007/s40484‑019‑0172‑y
     [Google Scholar]
  45. KumarA. KumarV. KumariK. JainP. KaushikN.K. SinghP. Promising iron(II) complexes of curcumins: Designing, density functional theory, and molecular docking.J. Phys. Org. Chem.2021347e419610.1002/poc.4196
     [Google Scholar]
  46. Saíz-UrraL. CabreraM.A. FroeyenM. Exploring the conformational changes of the ATP binding site of gyrase B from Escherichia coli complexed with different established inhibitors by using molecular dynamics simulation.J. Mol. Graph. Model.201129572673910.1016/j.jmgm.2010.12.005 21216167
     [Google Scholar]
  47. OmarM.A. MasaretG.S. AbbasE.M.H. Abdel-AzizM.M. HarrasM.F. FarghalyT.A. Novel anti-tubercular and antibacterial based benzosuberone-thiazole moieties: Synthesis, molecular docking analysis, DNA gyrase supercoiling and ATPase activity.Bioorg. Chem.202010410431610.1016/j.bioorg.2020.104316 33022549
     [Google Scholar]
  48. KashyapA. SinghP.K. SatpatiS. VermaH. SilakariO. Pharmacophore modeling and molecular dynamics approach to identify putative DNA Gyrase B inhibitors for resistant tuberculosis.J. Cell. Biochem.201912033149315910.1002/jcb.27579 30191589
     [Google Scholar]
  49. GhannamI.A.Y. Abd El-MeguidE.A. AliI.H. SheirD.H. El KerdawyA.M. Novel 2-arylbenzothiazole DNA gyrase inhibitors: Synthesis, antimicrobial evaluation, QSAR and molecular docking studies.Bioorg. Chem.20199310337310.1016/j.bioorg.2019.103373 31698294
     [Google Scholar]
  50. JukičM. IlašJ. BrvarM. KikeljD. CesarJ. AnderluhM. Linker-switch approach towards new ATP binding site inhibitors of DNA gyrase B.Eur. J. Med. Chem.201712550051410.1016/j.ejmech.2016.09.040 27689732
     [Google Scholar]
/content/journals/mc/10.2174/0115734064307744240523112710
Loading
New 3-Hydroxypyridine-4-one Analogues: Their Synthesis, Antimicrobial Evaluation, Molecular Docking, and In Silico ADME Prediction
Med. Chem. 20, 900 (2024); https://doi.org/10.2174/0115734064307744240523112710
/content/journals/mc/10.2174/0115734064307744240523112710
/content/journals/mc/10.2174/0115734064307744240523112710
Loading

Data & Media loading...

Supplements

file format download Download

  • Article Type:     Research Article
Keyword(s): 3-hydroxypyridine-4-one; ADME prediction; antibacterial; antifungal; molecular docking study; Synthesis

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