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Volume 32, Issue 9
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Aim

In this study, a neoteric and expedient oxidation method is applied for a variety of Hantzsch 1,4-dihydropyridine derivatives such as 1,4-dihydro-2,6-dimethyl-3,5-diacetylpyridine, 3,5-bis-hydrazono--2,6-dimethyl-1,4-dihydropyridine, and 3,5-bis-thiazoly-2,6-dimethyl-1,4-dihydro pyridines.

Methods

This simple oxidation is based upon the generation of nitrous acid from an aqueous sodium nitrite and acetic acid mixture and could be used to downgrade costs, sustain resources, and minimize chemical wastes. Also, a molecular modeling strategy was used to study the mechanism of action for various derivatives of bis-hydrazinylidene-thiazole as the protein Vascular Endothelial Growth Factor Receptor Tyrosine Kinase (VEGFR TK) inhibitor through evaluating their binding scores and modes compared with Sorafenib as a reference standard.

Results

The results revealed that the interaction of hydrazinylidene and thiazole as an anticancer Tyrosine Kinase inhibitor has been improved.

Conclusion

Additionally, the compounds exhibiting the highest activity were assessed for their potential anticancer effects against HepG-2, MCF-7, and WI-38 cells, and the outcomes demonstrated encouraging activity against cancer.

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2024-03-15
2025-04-22

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References

  1. OzerE.K. GunduzM.G. El-KhoulyA. SaraY. SimsekR. IskitA.B. SafakC. Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers.Turk Biyokim. Derg.201843657858610.1515/tjb‑2016‑0247
     [Google Scholar]
  2. SwarnalathaG. PrasanthiG. SirishaN. ChettyC.M. 1,4-dihydropyridines: A multtifunctional molecule : A review.Inter. J. Chem. Tech. Res201237589
     [Google Scholar]
  3. IdhayadhullaA. KumarR.S. NasserA.J.A. KavimaniS. IndhumathyS. Anti-inflammatory activity of new series of 1,4-dihydropyridine derivatives.Pharm. Chem. J.201549746346610.1007/s11094‑015‑1305‑x
     [Google Scholar]
  4. GomhaS.M. EdreesM.M. MuhammadZ.A. KhederN.A. Abu- MelhaS. SaadA.M. Synthesis, characterization, and antimicrobial evaluation of some new 1,4-dihydropyridines-1,2,4-triazole hybrid compounds.Polycycl. Aromat. Compd.202242117318510.1080/10406638.2020.1720751
     [Google Scholar]
  5. KrukI. KladnaA. LichszteldK. MichalskaT. Aboul-EneinH.Y. TunçbilekM. ErtanR. Antioxidant activity of 4-flavonil-1,4-dihydropyridine derivatives.Biopolymers200162316316710.1002/bip.101011343286
     [Google Scholar]
  6. Niranjan BabuM. ElumalaiK. SrinivasanS. EluriK. ElumalaiM. SivannanS. Synthesis and anticholinesterase activity of a novel series of acetazolamide condensed 1,4-dihydropyridines.Carbon. Resou. Conv.20192319119710.1016/j.crcon.2019.10.002
     [Google Scholar]
  7. PraveenkumarE. GurrapuN. Kumar KolluriP. YerraguntaV. Reddy KunduruB. SubhashiniN.J.P. Synthesis, anti-diabetic evaluation and molecular docking studies of 4-(1-aryl-1H-1, 2, 3-triazol-4-yl)-1,4-dihydropyridine derivatives as novel 11-β hydroxysteroid dehydrogenase-1 (11β-HSD1) inhibitors.Bioorg. Chem.20199010305610.1016/j.bioorg.2019.10305631276952
     [Google Scholar]
  8. GomhaS.M. MuhammadZ.A. Abdel-azizH.M. MatarI.K. El-SayedA.A. Green synthesis, molecular docking and anticancer activity of novel 1,4-dihydropyridine-3,5-Dicarbohydrazones under grind-stone chemistry.Green Chem. Lett. Rev.202013161710.1080/17518253.2019.1710268
     [Google Scholar]
  9. GomhaS.M. MuhammadZ.A. Ezz El-ArabE. ElmetwallyA.M. El-SayedA.A. MatarI.K. Design, synthesis, molecular docking study and anti-hepatocellular carcinoma evaluation of new bis-triazolothiadiazines.Mini Rev. Med. Chem.202020978880010.2174/138955751966619101513003731613728
     [Google Scholar]
  10. GomhaS.M. MuhammadZ.A. El-ReedyA.A.M. Intramolecular ring transformation of bis-oxadiazoles to bis-thiadiazoles and investigation of their anticancer activities.J. Heterocycl. Chem.201855102360236710.1002/jhet.3300
     [Google Scholar]
  11. ZhangD. MaY. LiuY. LiuZ.P. Synthesis of sulfonylhydrazone- and acylhydrazone-substituted 8-ethoxy-3-nitro-2H-chromenes as potent antiproliferative and apoptosis inducing agents.Arch. Pharm.2014347857658810.1002/ardp.20140008224866448
     [Google Scholar]
  12. IbrahimH.S. Abou-seriS.M. IsmailN.S.M. ElaasserM.M. AlyM.H. Abdel-AzizH.A. Bis-isatin hydrazones with novel linkers: Synthesis and biological evaluation as cytotoxic agents.Eur. J. Med. Chem.201610841542210.1016/j.ejmech.2015.11.04726706352
     [Google Scholar]
  13. ŞenkardeşS. TüreA. EkrekS. DurakA.T. AbbakM. ÇevikÖ. KaşkatepeB. Küçükgüzelİ. Güniz KüçükgüzelŞ. Novel 2,6-disubstituted pyridine hydrazones: Synthesis, anticancer activity, docking studies and effects on caspase-3-mediated apoptosis.J. Mol. Struct.2021122312896210.1016/j.molstruc.2020.128962
     [Google Scholar]
  14. ÖzkayY. Işıkdağİ. İncesuZ. AkalınG. Synthesis of 2-substituted-N-[4-(1-methyl-4,5-diphenyl-1H-imidazole-2-yl)phenyl]acetamide derivatives and evaluation of their anticancer activity.Eur. J. Med. Chem.20104583320332810.1016/j.ejmech.2010.04.01520451307
     [Google Scholar]
  15. SankarP.R. SailuA.B. MunnangiE. SatyaM.N. SreejaP. RojaP. RijwanaS.K. Analytical methods for determination of different members of FDA approved tyrosine kinase inhibitors like dasatinib, lapatinib, imatinib, sorafenib, nintedanib, sunitinib and pazopanib: A review.J. Pharm. Sci. Res202113313318
     [Google Scholar]
  16. BroekmanF. GiovannettiE. PetersG.J. Tyrosine kinase inhibitors: Multi-targeted or single-targeted?World J. Clin. Oncol.201122809310.5306/wjco.v2.i2.8021603317
     [Google Scholar]
  17. YangJ. YanJ. LiuB. Targeting VEGF/VEGFR to modulate antitumor immunity.Front. Immunol.2018997810.3389/fimmu.2018.0097829774034
     [Google Scholar]
  18. WangX. BoveA.M. SimoneG. MaB. Molecular bases of VEGFR-2-mediated physiological function and pathological role.Front. Cell Dev. Biol.2020859928110.3389/fcell.2020.59928133304904
     [Google Scholar]
  19. ModiS.J. KulkarniV.M. Vascular endothelial growth factor receptor (VEGFR-2)/KDR inhibitors: Medicinal chemistry perspective.Med. Drug. Disc.2019210000910.1016/j.medidd.2019.100009
     [Google Scholar]
  20. HashemiM.M. ZakeriM.S. ArianfarS. Oxidation of hantzsch 1,4- dihydropyridines to pyridines with thallium triacetate.J. Chem. Chem. Eng.200322911
     [Google Scholar]
  21. TamaddonF. RazmiZ. Oxidation of 1,4-dihydropyridines and 3,4-dihydropyrimidin-2(1 H )-ones to substituted pyridines and pyrimidinones using Ca(OCl)2 in aqueous media.Synth. Commun.201141448549210.1080/00397911003587523
     [Google Scholar]
  22. NikoorazmM. A new method for the oxidation of 1, 4-dihydropyridine derivatives by guanidinium nitrate in the presence of silica sulfuric acid under mild, heterogeneous and metal-free conditions.Scientia Iranica C201320603606
     [Google Scholar]
  23. BaiC.B. WangN.X. WangY.J. LanX.W. XingY. WenJ.L. A new oxidation system for the oxidation of Hantzsch-1,4-dihydropyridines and polyhydroquinoline derivatives under mild conditions.RSC Advances2015512210053110053410.1039/C5RA20977C
     [Google Scholar]
  24. ZafarA.M. JabeenM. AslamN. AnjumS. Abdul GhafoorK.M. Oxidation of some dihydropyridine derivatives to pyridine via different methods.Front. Chem. Sci2021211713110.52700/fcs.v2i2.22
     [Google Scholar]
  25. HanB. LiuZ. LiuQ. YangL. LiuZ.L. YuW. An efficient aerobic oxidative aromatization of Hantzsch 1,4-dihydropyridines and 1,3,5-trisubstituted pyrazolines.Tetrahedron200662112492249610.1016/j.tet.2005.12.056
     [Google Scholar]
  26. Abdel-MohsenH.T. ConradJ. BeifussU. Laccase-catalyzed oxidation of Hantzsch 1,4-dihydropyridines to pyridines and a new one pot synthesis of pyridines.Green Chem.201214102686269010.1039/c2gc35950b
     [Google Scholar]
  27. ZolfigolM.A. Kiany-borazjaniM. SadeghiM.M. MemarianH.R. Mohammadpoor-baltorkI. Oxidation of 1,4-dihydropyridines under mild and heterogeneous conditions.Synth. Commun.200030162945295010.1080/00397910008087444
     [Google Scholar]
  28. AbbasI. GomhaS. ElaasserM. BauomiM. Synthesis and biological evaluation of new pyridines containing imidazole moiety as antimicrobial and anticancer agents.Turk. J. Chem.20153933434610.3906/kim‑1410‑25
     [Google Scholar]
  29. GomhaS.M. MuhammadZ.A. Abdel-azizM.R. Abdel-azizH.M. GaberH.M. ElaasserM.M. One pot synthesis of new thiadiazolyl-pyridines as anticancer and antioxidant agents.J. Heterocycl. Chem.201855253053610.1002/jhet.3088
     [Google Scholar]
  30. Abdel-azizH.M. GomhaS.M. El-SayedA.A. MabkhotY.N. AlsayariA. MuhsinahA.B. Facile synthesis and antiproliferative activity of new 3-cyanopyridines.BMC Chem.201913113710.1186/s13065‑019‑0652‑131891163
     [Google Scholar]
  31. RashdanH.R.M. GomhaS.M. El-GendeyM.S. El-HashashM.A. SolimanA.M.M. Eco-friendly one-pot synthesis of some new pyrazolo[1,2- b ]phthalazinediones with antiproliferative efficacy on human hepatic cancer cell lines.Green Chem. Lett. Rev.201811326427410.1080/17518253.2018.1474270
     [Google Scholar]
  32. BadreyM.G. GomhaS.M. 3-Amino-8-hydroxy-4-imino-6-methyl-5-phenyl-4,5-dihydro-3H-chromeno[2,3-d]pyrimidine: An effecient key precursor for novel synthesis of some interesting triazines and triazepines as potential anti-tumor agents.Molecules20121710115381155310.3390/molecules17101153823018926
     [Google Scholar]
  33. GomhaS.M. Abdel-azizH.M. Synthesis and antitumor activity of 1,3,4-thiadiazole derivatives bearing coumarine ring.Heterocycles20159158359210.3987/COM‑14‑13146
     [Google Scholar]
  34. GomhaS.M. EdreesM.M. FatyR.A.M. MuhammadZ.A. MabkhotY.N. Microwave-assisted one pot three-component synthesis of some novel pyrazole scaffolds as potent anticancer agents.Chem. Cent. J.20171113710.1186/s13065‑017‑0266‑429086808
     [Google Scholar]
  35. IbrahimM.S. FaragB. Al-HumaidiJ. ZakiM.E.A. FathallaM. GomhaS.M. Mechanochemical synthesis and molecular docking studies of new azines bearing indole as anticancer agents.Molecules2023289386910.3390/molecules2809386937175279
     [Google Scholar]
  36. Abu-MelhaS. EdreesM. SalemH. KhederN. GomhaS. AbdelazizM. Synthesis and biological evaluation of some novel thiazole-based heterocycles as potential anticancer and antimicrobial agents.Molecules201924353910.3390/molecules2403053930717217
     [Google Scholar]
  37. GomhaS.M. RiyadhS.M. MahmmoudE.A. ElaasserM.M. Synthesis and anticancer activities of thiazoles, 1,3-thiazines, and thiazolidine using chitosan-grafted-poly(vinylpyridine) as basic catalyst.Heterocycles2015911227124310.3987/COM‑15‑13210
     [Google Scholar]
  38. AsgaonkarK. TanksaliS. AbhangK. SagarA. Development of optimized pyrimido-thiazole scaffold derivatives as anticancer and multitargeting tyrosine kinase inhibitors using computational studies.J. Indian Chem. Soc.2023100110080310.1016/j.jics.2022.100803
     [Google Scholar]
  39. McTigueM. MurrayB.W. ChenJ.H. DengY.L. SolowiejJ. KaniaR.S. Molecular conformations, interactions, and properties associated with drug efficiency and clinical performance among VEGFR TK inhibitors.Proc. Natl. Acad. Sci.201210945182811828910.1073/pnas.120775910922988103
     [Google Scholar]
  40. LabuteP. Protonate3D: Assignment of ionization states and hydrogen coordinates to macromolecular structures.Proteins200975118720510.1002/prot.2223418814299
     [Google Scholar]
  41. KattanS.W. NafieM.S. ElmgeedG.A. AlelwaniW. BadarM. TantawyM.A. Molecular docking, anti-proliferative activity and induction of apoptosis in human liver cancer cells treated with androstane derivatives: Implication of PI3K/AKT/mTOR pathway.J. Steroid Biochem. Mol. Biol.202019810560410.1016/j.jsbmb.2020.10560431982513
     [Google Scholar]
  42. TantawyM.A. SroorF.M. MohamedM.F. El-NaggarM.E. SalehF.M. HassaneenH.M. AbdelhamidI.A. Molecular docking study, cytotoxicity, cell cycle arrest and apoptotic induction of novel chalcones incorporating thiadiazolyl isoquinoline in cervical cancer.Anticancer. Agents Med. Chem.2020201708310.2174/187152061966619102412111631696811
     [Google Scholar]
  43. NafieM.S. TantawyM.A. ElmgeedG.A. Screening of different drug design tools to predict the mode of action of steroidal derivatives as anti-cancer agents.Steroids201915210848510.1016/j.steroids.2019.10848531491446
     [Google Scholar]
  44. KurfürstA. TrškaP. GoljerI. Interpretation of 13C NMR chemical shifts of Hantzsch’s pyridines and 1,4-dihydropyridines.Collect. Czech. Chem. Commun.198449102393239910.1135/cccc19842393
     [Google Scholar]
  45. KulakovI.V. KarbainovaA.A. ShulgauZ.T. SeilkhanovT.M. GatilovY.V. FisyukA.S. Synthesis and analgesic activity of bis(3,4-dihydroquinoxalin-2(1H)-one) and bis(3,4-dihydro-2H-1,4-benzoxazin-2-one) derivatives.Chem. Heterocycl. Compd.201753101094109710.1007/s10593‑017‑2178‑6
     [Google Scholar]
  46. ZhuX.Q. ZhaoB.J. ChengJ.P. Mechanisms of the oxidations of NAD(P)H model Hantzsch 1,4-dihydropyridines by nitric oxide and its donor N-methyl-N-nitrosotoluene-p-sulfonamide.J. Org. Chem.200065248158816310.1021/jo000484h11101368
     [Google Scholar]
  47. GreenbaumD.C. MackeyZ. HansellE. DoyleP. GutJ. CaffreyC.R. LehrmanJ. RosenthalP.J. McKerrowJ.H. ChibaleK. Synthesis and structure-activity relationships of parasiticidal thiosemicarbazone cysteine protease inhibitors against Plasmodium falciparum, Trypanosoma brucei, and Trypanosoma cruzi. J. Med. Chem.200447123212321910.1021/jm030549j15163200
     [Google Scholar]
  48. AbbasI.M. RiyadhS.M. AbdallahM.A. GomhaS.M. A novel route to tetracyclic fused tetrazines and thiadiazines.J. Heterocycl. Chem.200643493594210.1002/jhet.5570430419
     [Google Scholar]
  49. GomhaS.M. FarghalyT.A. AbbasE.M.H. AlqurashiN.T. Terephthalaldehyde: An efficient key precursor for novel synthesis of some interesting bis-thiazoles and bis-triazolopyrimidinones.J. Heterocycl. Chem.201855375075510.1002/jhet.3100
     [Google Scholar]
  50. OleshchukA.L. KarbainovaA.A. KrivoruchkoT.N. ShulgauZ.T. SeilkhanovT.M. KulakovI.V. Synthesis and biological activity of 3,5-diacetyl-2,6-dimethylpyridine derivatives.Chem. Heterocycl. Compd.2019551475110.1007/s10593‑019‑02417‑5
     [Google Scholar]
  51. LvP.C. LiD.D. LiQ.S. LuX. XiaoZ.P. ZhuH.L. Synthesis, molecular docking and evaluation of thiazolyl-pyrazoline derivatives as EGFR TK inhibitors and potential anticancer agents.Bioorg. Med. Chem. Lett.201121185374537710.1016/j.bmcl.2011.07.01021802290
     [Google Scholar]
  52. AbolibdaT.Z. FathallaM. FaragB. ZakiM.E.A. GomhaS.M. Synthesis and molecular docking of some novel 3-thiazolyl-coumarins as inhibitors of VEGFR-2 kinase.Molecules202328268910.3390/molecules2802068936677750
     [Google Scholar]
  53. BhanushaliU. RajendranS. SarmaK. KulkarniP. ChattiK. ChatterjeeS. RamaaC.S. 5-Benzylidene-2,4-thiazolidenedione derivatives: Design, synthesis and evaluation as inhibitors of angiogenesis targeting VEGR-2.Bioorg. Chem.20166713914710.1016/j.bioorg.2016.06.00627388635
     [Google Scholar]
  54. GomhaS. SalaheldinT. HassaneenH. Abdel-AzizH. KhedrM. Synthesis, characterization and molecular docking of novel bioactive thiazolyl-thiazole derivatives as promising cytotoxic antitumor drug.Molecules2015211310.3390/molecules2101000326703554
     [Google Scholar]
  55. DingH. ChenZ. ZhangC. XinT. WangY. SongH. JiangY. ChenY. XuY. TanC. Synthesis and cytotoxic activity of some novel N-pyridinyl-2-(6-phenylimidazo[2,1-b]thiazol-3-yl)acetamide derivatives.Molecules20121744703471610.3390/molecules1704470322525437
     [Google Scholar]
  56. AshmawyF.O. GomhaS.M. AbdallahM.A. ZakiM.E.A. Al-HussainS.A. El-desoukyM.A. Synthesis, in vitro evaluation and molecular docking studies of novel thiophenyl thiazolyl-pyridine hybrids as potential anticancer agents.Molecules20232811427010.3390/molecules2811427037298747
     [Google Scholar]
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Synthesis of Bis-thiazoles Tethered 1,4-Dihydropyridine and Pyridine Linkers <span class="jp-italic">&nbsp;via</span> Simple Oxidation and their Molecular Docking as VEGFR-TK Inhibitors
Curr. Med. Chem. 32, 1789 (2025); https://doi.org/10.2174/0109298673266044231002071238
/content/journals/cmc/10.2174/0109298673266044231002071238
/content/journals/cmc/10.2174/0109298673266044231002071238
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  • Article Type:     Research Article
Keyword(s): 1,4-dihydropyridines; anticancer; hydrazonoyl halides; molecular docking; nitrous acid; Oxidation; SAR; VEGFR-2 inhibitors

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