Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Organic Chemistry
  4. Volume 29, Issue 4
  5. Article
Volume 29, Issue 4
  • ISSN: 1385-2728
  • E-ISSN: 1875-5348

Abstract

An efficient protocol is reported for synthesizing arylidene adducts, pyridine derivatives, in excellent yields by treating 2-cyano--(4-(1-(2-(2-cyanoacetyl) hydrazineylidene)ethyl)phenyl)acetamide with quinoline-3-carbaldehydes, 2-arylidenemalono-nitriles, and acetylacetone in EtOH, respectively. In addition, dithiadiazole and dithiophene adducts were synthesized from one pot reaction using phenyl isothiocyanate, and either hydrazonyl chloride or 2-bromo-1-(5-methyl-1-(-tolyl)-1-1,2,3-triazole-4-yl)ethan-1-one in DMF containing potassium hydroxide. The structure of novel products was elucidated using spectroscopic data and elemental analyses. The synthesized compounds were evaluated for their antimicrobial activities. The compounds showed antibacterial and antifungal activities against the tested G-ve and G+ve bacteria and against the tested fungi. The MIC was mostly in the range of 100-500 µg/mL. Molecular docking was used to analyse interactions between the compounds and antimicrobial target proteins. The molecular docking simulation showed lower binding energy with different types of interaction at the active site of Sterol 14-demethylase of , Fdc1 proteins of DNA Gyrase of and LasR, an activator of exotoxin. An expression of indicates that these compounds could inhibit the enzyme and cause promising antimicrobial effects.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/coc/10.2174/0113852728331650240828101111
2025-09-20
2025-01-18

  • From This Site

    /content/journals/coc/10.2174/0113852728331650240828101111
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. AlmarhoonZ. Al RasheedH.H. El-FahamA. Ultrasonically assisted N-cyanoacylation and synthesis of Alkyl(4-(3-cyano-4,6-dimethyl-2-oxopy-ridin-1(2 H)-yl)benzoyl)amino acid ester derivatives.ACS Omega2020547306713067810.1021/acsomega.0c04730 33283115
     [Google Scholar]
  2. KhidreR.E. RadiniI.A.M. IbrahimaD.A. Synthesis of a novel heterocyclic scaffold utilizing 2-cyano-N-(3-cyano-4,6-dimethyl-2-oxopyridin-1-yl) acetamide.ARKIVOC20162016530131710.3998/ark.5550190.p009.722
     [Google Scholar]
  3. Abdel-MegidM. A convenient route for the synthesis of some new bi- and triheterocondensed uracils.Chem. Heterocycl. Compd.201046331632410.1007/s10593‑010‑0507‑0
     [Google Scholar]
  4. SilvaG.A. CostaL.M.M. BritoF.C.F. MirandaA.L.P. BarreiroE.J. FragaC.A.M. New class of potent antinociceptive and antiplatelet 10H-phenothiazine-1-acylhydrazone derivatives.Bioorg. Med. Chem.200412123149315810.1016/j.bmc.2004.04.009 15158783
     [Google Scholar]
  5. NasrT. BondockS. EidS. Design, synthesis, antimicrobial evaluation and molecular docking studies of some new thiophene, pyrazole and pyridone derivatives bearing sulfisoxazole moiety.Eur. J. Med. Chem.20148449150410.1016/j.ejmech.2014.07.052 25050881
     [Google Scholar]
  6. DemjénA. AlföldiR. AngyalA. GyurisM. HacklerL.Jr SzebeniG.J. WölflingJ. PuskásL.G. KanizsaiI. Synthesis, cytotoxic characterization, and SAR study of imidazo[1,2‐b]pyrazole‐7‐carboxamides.Arch. Pharm. (Weinheim)20183517180006210.1002/ardp.201800062 29888449
     [Google Scholar]
  7. MetwallyN.H. AbdelrazekF.M. EldalyS.M. MetzP. 3-(3,5-dimethyl-1H-Pyrazol-1-yl)-3-oxopropanenitrile as precursor for some new mono-heterocyclic and bis-heterocyclic compounds.J. Heterocycl. Chem.201754128929410.1002/jhet.2578
     [Google Scholar]
  8. ChigorinaE.A. DotsenkoV.V. 1-Cyanoacetyl-3,5-dimethylpyrazole– effective cyanoacetylating agent and a new building block for the synthesis of heterocyclic compounds. (Review)Chem. Heterocycl. Compd.201248811331152 [Review].10.1007/s10593‑012‑1116‑x
     [Google Scholar]
  9. ChigorinaE. 1-Cyanoacetyl-3,5-dimethylpyrazole.Synlett201325345345410.1055/s‑0033‑1340469
     [Google Scholar]
  10. AbumelhaH.M.A. Synthesis and antioxidant assay of new nicotinonitrile analogues clubbed thiazole, pyrazole and/or pyridine ring systems.J. Heterocycl. Chem.20205731011102210.1002/jhet.3820
     [Google Scholar]
  11. KapingS. BoissI. SinghaL.I. HelisseyP. VishwakarmaJ.N. A facile, regioselective synthesis of novel 3-(N-phenylcarboxamide)pyrazolo[1,5-a]pyrimidine analogs in the presence of KHSO4 in aqueous media assisted by ultrasound and their antibacterial activities.Mol. Divers.201620237939010.1007/s11030‑015‑9639‑6 26511367
     [Google Scholar]
  12. TorabiM. YarieM. BagheryS. ZolfigolM.A. Recent advances in catalytic synthesis of pyridine derivatives. Singh, P. Recent Developments in the Synthesis and Applications of Pyridines.Elsevier202350358010.1016/B978‑0‑323‑91221‑1.00002‑6
     [Google Scholar]
  13. AlizadehS.R. EbrahimzadehM.A. Antiviral activities of pyridine fused and pyridine containing heterocycles, a review (from 2000 to 2020).Mini Rev. Med. Chem.202121172584261110.2174/18755607MTEzvNjcu0 33573543
     [Google Scholar]
  14. AltafA.A. ShahzadA. GulZ. RasoolN. BadshahA. LalB. KhanE. A review on the medicinal importance of pyridine derivatives.J. Drug Design Med. Chem.2015111110.11648/j.jddmc.20150101.11
     [Google Scholar]
  15. DeS. KumarS.K. A.; Shah, S.K.; Kazi, S.; Sarkar, N.; Banerjee, S.; Dey, S. Pyridine: The scaffolds with significant clinical diversity.RSC Advances20221224153851540610.1039/D2RA01571D 35693235
     [Google Scholar]
  16. KhidreR.E. Abdel-WahabB.F. Application of benzoylaceteonitrile in the synthesis of pyridines derivatives.Curr. Org. Chem.20131743044510.2174/1385272811317040009
     [Google Scholar]
  17. MohamedE.A. IsmailN.S.M. HagrasM. RefaatH. Medicinal attributes of pyridine scaffold as anticancer targeting agents.Future J. Pharm. Sci.2021712410.1186/s43094‑020‑00165‑4
     [Google Scholar]
  18. AliabadiA. MotieiyanE. HosseinabadiF. GhadermaziM. AbdolmalekiS. One-pot synthesis, crystallographic characterization, evaluation as in vitro antibacterial and cytotoxic agents of two mercury(II) complexes containing pyridine dicarboxylic acid derivatives.J. Mol. Struct.2021122612940510.1016/j.molstruc.2020.129405
     [Google Scholar]
  19. AliE.M.H. Abdel-MaksoudM.S. HassanR.M. MersalK.I. AmmarU.M. Se-InC. He-SooH. KimH.K. LeeA. LeeK.T. OhC.H. Design, synthesis and anti-inflammatory activity of imidazol-5-yl pyridine derivatives as p38α/MAPK14 inhibitor.Bioorg. Med. Chem.20213111596910.1016/j.bmc.2020.115969 33422910
     [Google Scholar]
  20. BassA. AbdelhafezE. El-ZoghbiM. MohamedM. BadrM. Abuo-RahmaG.E.D. 3-Cyano-2-oxa-pyridines: A promising template for diverse pharmacological activities.J. Adv. Biomedical Pharm. Sci.202142818610.21608/jabps.2020.52641.1113
     [Google Scholar]
  21. HammoudiN.E.H. BenguerbaY. AttouiA. HognonC. LemaouiT. SobhiW. BenaichaM. BadawiM. MonariA. In silico drug discovery of IKK-β inhibitors from 2-amino-3-cyano-4-alkyl-6-(2-hydroxyphenyl) pyridine derivatives based on QSAR, docking, molecular dynamics and drug-likeness evaluation studies.J. Biomol. Struct. Dyn.202240288690210.1080/07391102.2020.1819878 32948119
     [Google Scholar]
  22. SugiyamaS. AkiyamaT. TaodaY. IwakiT. MatsuokaE. AkihisaE. SekiT. YoshinagaT. KawasujiT. Discovery of novel HIV-1 integrase-LEDGF/p75 allosteric inhibitors based on a pyridine scaffold forming an intramolecular hydrogen bond.Bioorg. Med. Chem. Lett.20213312774210.1016/j.bmcl.2020.127742 33316407
     [Google Scholar]
  23. ArchnaPathania. S.; Chawla, P.A. Thiophene-based derivatives as anticancer agents: An overview on decade’s work.Bioorg. Chem.202010110402610.1016/j.bioorg.2020.104026 32599369
     [Google Scholar]
  24. ShahR. VermaP.K. Synthesis of thiophene derivatives and their anti-microbial, antioxidant, anticorrosion and anticancer activity.BMC Chem.20191315410.1186/s13065‑019‑0569‑8 31384802
     [Google Scholar]
  25. ShahR. VermaP.K. Therapeutic importance of synthetic thiophene.Chem. Cent. J.201812113710.1186/s13065‑018‑0511‑5 30564984
     [Google Scholar]
  26. SinghA. SinghG. BediP.M.S. Thiophene derivatives: A potent multitargeted pharmacological scaffold.J. Heterocycl. Chem.20205772658270310.1002/jhet.3990
     [Google Scholar]
  27. RassuG. ZanardiF. BattistiniL. CasiraghiG. The synthetic utility of furan-, pyrrole- and thiophene-based 2-silyloxy dienes.Chem. Soc. Rev.200029210911810.1039/a900200f
     [Google Scholar]
  28. BarbarellaG. ZangoliM. MariaF.D. Chapter three - synthesis and applications of thiophene derivatives as organic materials.Advances in Heterocyclic ChemistryAcademic Press201712310516710.1016/bs.aihch.2017.01.001
     [Google Scholar]
  29. GuoL. SafiZ.S. KayaS. ShiW. TüzünB. AltunayN. KayaC. Anticorrosive effects of some thiophene derivatives against the corrosion of iron: A computational study.Front Chem.2018615510.3389/fchem.2018.00155 29868558
     [Google Scholar]
  30. SperryJ.B. WrightD.L. Thiophenes and related heterocycles in drug discovery.Curr. Opin. Drug Discov. Dev.20058723740
     [Google Scholar]
  31. MishraA. MaC.Q. BäuerleP. Functional oligothiophenes: Molecular design for multidimensional nanoarchitectures and their applications.Chem. Rev.200910931141127610.1021/cr8004229 19209939
     [Google Scholar]
  32. OrtizR.P. CasadoJ. HernándezV. NavarreteJ.T.L. LetiziaJ.A. RatnerM.A. FacchettiA. MarksT.J. Cover picture: Thiophene–diazine molecular semiconductors: synthesis, structural, electrochemical, optical, and electronic structural properties; implementation in organic field‐effect transistors (Chem. Eur. J. 20/2009).Chemistry200915204959495910.1002/chem.200990069
     [Google Scholar]
  33. JanowskaS. KhylyukD. BielawskaA. SzymanowskaA. GornowiczA. BielawskiK. NoworólJ. MandziukS. WujecM. New 1,3,4-thiadiazole derivatives with anticancer activity.Molecules2022276181410.3390/molecules27061814 35335177
     [Google Scholar]
  34. OthmanA.A. KihelM. AmaraS. 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole derivatives as potential antibacterial agents.Arab. J. Chem.20191271660167510.1016/j.arabjc.2014.09.003
     [Google Scholar]
  35. ChenJ. YiC. WangS. WuS. LiS. HuD. SongB. Novel amide derivatives containing 1,3,4-thiadiazole moiety: Design, synthesis, nematocidal and antibacterial activities.Bioorg. Med. Chem. Lett.201929101203121010.1016/j.bmcl.2019.03.017 30902458
     [Google Scholar]
  36. KhanI. AliS. HameedS. RamaN.H. HussainM.T. WadoodA. UddinR. Ul-HaqZ. KhanA. AliS. ChoudharyM.I. Synthesis, antioxidant activities and urease inhibition of some new 1,2,4-triazole and 1,3,4-thiadiazole derivatives.Eur. J. Med. Chem.201045115200520710.1016/j.ejmech.2010.08.034 20828889
     [Google Scholar]
  37. JatavV. MishraP. KashawS. StablesJ.P. CNS depressant and anticonvulsant activities of some novel 3-[5-substituted 1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3H)-ones.Eur. J. Med. Chem.20084391945195410.1016/j.ejmech.2007.12.003 18222569
     [Google Scholar]
  38. ClericiF. PocarD. GuidoM. LocheA. PerliniV. BrufaniM. Synthesis of 2-amino-5-sulfanyl-1,3,4-thiadiazole derivatives and evaluation of their antidepressant and anxiolytic activity.J. Med. Chem.200144693193610.1021/jm001027w 11300875
     [Google Scholar]
  39. NoolviM.N. PatelH.M. SinghN. GadadA.K. CameotraS.S. BadigerA. Synthesis and anticancer evaluation of novel 2-cyclopropylimidazo[2,1-b][1,3,4]-thiadiazole derivatives.Eur. J. Med. Chem.20114694411441810.1016/j.ejmech.2011.07.012 21820217
     [Google Scholar]
  40. KhidreR.E. El-GogaryS.R. MostafaM.S. Design, synthesis, and antimicrobial evaluation of some novel pyridine, coumarin, and thiazole derivatives.J. Heterocycl. Chem.20175442511251910.1002/jhet.2854
     [Google Scholar]
  41. MostafaM.S. Abd El-SalamN.M. AlothmanO.Y. Synthesis and microbial activity of novel 3-methyl-2-pyrazolin-5-one derivatives.J. Chem.201320131710.1155/2013/183130
     [Google Scholar]
  42. AbouzayedF.I. MostafaM. S. HammadA.M. GhazalB. Abouel-EneinS. A. Synthesis, characterization, thermal, anticancer studies, and density functional theory for potentially active pyrimidine-based complexes. Appl. Organomet. Chem., 2024e739511910.1002/aoc.7395
     [Google Scholar]
  43. MalikA.N. AliA. AshfaqM. TahirM.N. AlamM.M. MostafaM.S. KuznetsovA. A synthetic approach towards drug modification: 2-hydroxy-1-naphthaldehyde based imine-zwitterion preparation, single-crystal study, Hirshfeld surface analysis, and computational investigation.RSC Advances202414106476649310.1039/D3RA08727A 38390507
     [Google Scholar]
  44. KhidreR.E. MostafaM.S. MukhrishY.E. SalemM.A. BehaloM.S. Synthetic methods of 1H-pyrazolo[1,2-b]phthalazine derivatives.Curr. Org. Chem.202326222055206910.2174/1385272827666230124145625
     [Google Scholar]
  45. BorikR.M. MostafaM.S. BehaloM.S. KhidreR.E. Recent progress in the synthetic methods of pyrazoloquinoline derivatives.Curr. Org. Chem.202428211713310.2174/0113852728285959240108060645
     [Google Scholar]
  46. MostafaM.S. RadiniI.A.M. El-RahmanN.M.A. KhidreR.E. Synthetic methods and pharmacological potentials of triazolothiadiazines: A review.Molecules2024296132610.3390/molecules29061326 38542962
     [Google Scholar]
  47. MetwallyN.H. AbdelrazekF.M. EldalyS.M. MetzP. 3‐(3,5‐dimethyl‐1 H‐pyrazol‐1‐yl)‐3‐oxopropanenitrile as precursor for some new mono‐heterocyclic and bis‐heterocyclic compounds.J. Heterocycl. Chem.201754128929410.1002/jhet.2578
     [Google Scholar]
  48. KhidreR.E. RadiniI.A.M. IbrahimD.A. Design and synthesis of some new thiophene and 1,3,4-thiadiazole based heterocycles.Phosphorus Sulfur Silicon Relat. Elem.2019194111040104710.1080/10426507.2019.1598408
     [Google Scholar]
  49. KlimešováV. SvobodaM. WaisserK. PourM. KaustováJ. New pyridine derivatives as potential antimicrobial agents.Farmaco1999541066667210.1016/S0014‑827X(99)00078‑6 10575735
     [Google Scholar]
  50. KhidreR.E. RadiniI.A.M. Design, synthesis and docking studies of novel thiazole derivatives incorporating pyridine moiety and assessment as antimicrobial agents.Sci. Rep.2021111784610.1038/s41598‑021‑86424‑7 33846389
     [Google Scholar]
  51. MandawadG.G. KambleR.D. HeseS.V. MoreR.A. GaccheR.N. KodamK.M. DawaneB.S. An efficient synthesis of isoxazoline libraries of thiophene analogs and its antimycobacterial investigation.Med. Chem. Res.201423104455446310.1007/s00044‑014‑1016‑y
     [Google Scholar]
  52. RomanG. Thiophene‐containing compounds with antimicrobial activity.Arch. Pharm. (Weinheim)20223556210046210.1002/ardp.202100462 35289443
     [Google Scholar]
  53. HafezH.N. HusseinH.A.R. El-GazzarA.R.B.A. Synthesis of substituted thieno[2,3-d]pyrimidine-2,4-dithiones and their S-glycoside analogues as potential antiviral and antibacterial agents.Eur. J. Med. Chem.20104594026403410.1016/j.ejmech.2010.05.060 20691339
     [Google Scholar]
  54. KhidreR.E. SabryE. El-SayedA.F. SediekA.A. Design, one-pot synthesis, in silico ADMET prediction and molecular docking of novel triazolyl thiadiazine and thiazole derivatives with evaluation of antimicrobial, antioxidant and antibiofilm inhibition activity.J. Iran. Chem. Soc.202320122923294710.1007/s13738‑023‑02889‑5
     [Google Scholar]
  55. SroorF.M. El‐SayedA.F. AbdelraofM. Design, synthesis, structure elucidation, antimicrobial, molecular docking, and SAR studies of novel urea derivatives bearing tricyclic aromatic hydrocarbon rings.Arch. Pharm.2024e230073810.1002/ardp.202300738
     [Google Scholar]
  56. JawhariA.H. MukhrishY.E. El-SayedA.F. Design, synthesis, in silico ADMET prediction, molecular docking, antimicrobial and antioxidant evaluation of novel diethyl pyridinyl phosphonate derivatives.Curr. Org. Chem.2023271086087510.2174/1385272827666230809094204
     [Google Scholar]
  57. El-SayedA.F. MohammedA.T. HamedW. AbdelmalekS. Repurposing of available antiviral drugs against SARS-CoV-2 by targeting crucial replication machinery proteins: A molecular docking study.Egypt. Pharm. J.202120437139210.4103/epj.epj_70_21
     [Google Scholar]
  58. JahangirianH. HaronJ. IsmailM.H.S. MoghaddamR.R. HejriL.A. AbdollahiY. RezayiM. VafaeiN. Well diffusion method for evaluation of antibacterial activity of copper phenyl fatty hydroxamate synthesized from canola and palm kernel oils.Dig. J. Nanomater. Biostruct.20138312631270
     [Google Scholar]
  59. WiegandI. HilpertK. HancockR.E.W. Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances.Nat. Protoc.20083216317510.1038/nprot.2007.521 18274517
     [Google Scholar]
  60. O’BoyleN.M. BanckM. JamesC.A. MorleyC. VandermeerschT. HutchisonG.R. Open Babel: An open chemical toolbox.J. Cheminform.2011313310.1186/1758‑2946‑3‑33 21982300
     [Google Scholar]
  61. EberhardtJ. Santos-MartinsD. TillackA.F. ForliS. AutoDock Vina 1.2.0: New docking methods, expanded force field, and python bindings.J. Chem. Inf. Model.20216183891389810.1021/acs.jcim.1c00203 34278794
     [Google Scholar]
  62. DainaA. MichielinO. ZoeteV. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules.Sci. Rep.2017714271710.1038/srep42717 28256516
     [Google Scholar]
/content/journals/coc/10.2174/0113852728331650240828101111
Loading
Design, Synthesis, Antimicrobial Activity and Molecular Docking of Novel Pyridine, Thiophene, and Thiadiazole Scaffolds Utilizing 2-Cyano-N-(4-(1-(2-(2-cyanoacetyl) hydrazineylidene)ethyl)phenyl)acetamide
Current Organic Chemistry 29, 311 (2025); https://doi.org/10.2174/0113852728331650240828101111
/content/journals/coc/10.2174/0113852728331650240828101111
/content/journals/coc/10.2174/0113852728331650240828101111
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): 2-cyano-N-(4-(1-(2-(2-cyanoacetyl)hydrazineylidene)ethyl)phenyl)acetamide; antimicrobial activity; docking; pyridine; thiadiazole; thiophene

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