Skip to content
2000
Volume 29, Issue 7
  • ISSN: 1385-2728
  • E-ISSN: 1875-5348

Abstract

A novel series of 4-[3-acetyl-2-(N-alkyl(aryl)acetamido)-1,3,4-thiadiazol-5-yl]-3-(2-oxo-2-chromen-3-yl)-1-(4-phenylthiazol-2-yl)-1-pyrazoles () and was synthesized in good yields. The methodology was depended on a one-pot four-components reaction of hydrazine hydrate, alkyl(aryl) isothiocyanate, 3-(2-oxo-2-chromen-3-yl)-1-(4-phenylthiazol-2-yl)-1-pyrazole-4-carboxaldehyde (), and acetic anhydride in acetic acid under ultrasound irradiation. The spectral tools confirmed the structures of all synthesized compounds. Using the standard SRB method, the designed compounds were screened for their cytotoxicity properties against PC3, HepG2, and HCT116 human cancer cell lines. Products and worked best against all cancer cells tested, as well as doxorubicin. Apoptosis and cell cycle analyses were performed for the bioactive products and . Both products strongly impacted all tumor cells in the late apoptotic pathway and significantly inhibited all cancer cell types under investigation in both the S and G2 phases. After that, a molecular docking study was carried out on products and to investigate how they interact with the CDK-8 receptor. The ADMET prediction suggested that these bioactive products may be effective anticancer treatments.

Loading

Article metrics loading...

/content/journals/coc/10.2174/0113852728326529240830101731
2024-09-19
2025-05-24
Loading full text...

Full text loading...

References

  1. MohamedN.G. ShehaM.M. HassanH.Y. Abdel-HafezL.J.M. OmarF.A. Synthesis, antimicrobial activity and molecular modeling study of 3-(5-amino-(2H)-1,2,4-triazol-3-yl]-naphthyridinones as potential DNA-gyrase inhibitors.Bioorg. Chem.20188159961110.1016/j.bioorg.2018.08.031 30248511
    [Google Scholar]
  2. KomeilizadethH. Does nature prefer heterocycles?Iran. J. Pharm. Res.20104229230
    [Google Scholar]
  3. HaqueI.U. Vinblastine: A review.J. Chem. Soc. Pak.20102245258
    [Google Scholar]
  4. SaidM. ElshihawyH. Synthesis, anticancer activity and structure-activity relationship of some anticancer agents based on cyclopenta (b) thiophene scaffold.Pak. J. Pharm. Sci.2014274885892 25015456
    [Google Scholar]
  5. El-sayedM.T. HamdyN.A. OsmanD.A. AhmedK.M. AhmedK.M. AhmedK.M. Indoles as anticancer agents.Adv. Mod. Oncol. Res.201511202510.18282/amor.v1.i1.12
    [Google Scholar]
  6. PlechT. WujecM. KosikowskaU. MalmA. RajtarB. Polz-DacewiczM. Synthesis and in vitro activity of 1,2,4-triazole-ciprofloxacin hybrids against drug-susceptible and drug-resistant bacteria.Eur. J. Med. Chem.20136012813410.1016/j.ejmech.2012.11.040 23287058
    [Google Scholar]
  7. YadavA.K. Maharjan ShresthaR. YadavP.N. Anticancer mechanism of coumarin-based derivatives.Eur. J. Med. Chem.202426711617910.1016/j.ejmech.2024.116179 38340509
    [Google Scholar]
  8. BalewskiŁ. SzultaS. JalińskaA. KornickaA. A mini-review: Recent advances in coumarin-metal complexes with biological properties.Front Chem.2021978177910.3389/fchem.2021.781779 34926402
    [Google Scholar]
  9. Sharifi-RadJ. Cruz-MartinsN. López-JornetP. LopezE.P.F. HarunN. YeskaliyevaB. BeyatliA. SytarO. ShaheenS. SharopovF. TaheriY. DoceaA.O. CalinaD. ChoW.C. Natural coumarins: Exploring the pharmacological complexity and underlying molecular mechanisms.Oxid. Med. Cell. Longev.202120211649234610.1155/2021/6492346 34531939
    [Google Scholar]
  10. AlipourM. KhoobiM. MoradiA. NadriH. Homayouni MoghadamF. EmamiS. HasanpourZ. ForoumadiA. ShafieeA. Synthesis and anti-cholinesterase activity of new 7-hydroxycoumarin derivatives.Eur. J. Med. Chem.20148253654410.1016/j.ejmech.2014.05.056 24941128
    [Google Scholar]
  11. ShikishimaY. TakaishiY. HondaG. ItoM. TakedaY. KodzhimatovO.K. AshurmetovO. LeeK.H. Chemical constituents of Prangos tschiniganica; structure elucidation and absolute configuration of coumarin and furanocoumarin derivatives with anti-HIV activity.Chem. Pharm. Bull. (Tokyo)200149787788010.1248/cpb.49.877 11456095
    [Google Scholar]
  12. ManjunathaM. NaikV.H. KulkarniA.D. PatilS.A. DNA cleavage, antimicrobial, anti-inflammatory anthelmintic activities, and spectroscopic studies of Co(II), Ni(II), and Cu(II) complexes of biologically potential coumarin Schiff bases.J. Coord. Chem.201164244264427510.1080/00958972.2011.621082
    [Google Scholar]
  13. KhoobiM. ForoumadiA. EmamiS. SafaviM. DehghanG. AlizadehB.H. RamazaniA. ArdestaniS.K. ShafieeA. Coumarin-based bioactive compounds: facile synthesis and biological evaluation of coumarin-fused 1,4-thiazepines.Chem. Biol. Drug Des.201178458058610.1111/j.1747‑0285.2011.01175.x 21740531
    [Google Scholar]
  14. SashidharaK.V. KumarA. ChatterjeeM. RaoK.B. SinghS. VermaA.K. PalitG. Discovery and synthesis of novel 3-phenylcoumarin derivatives as antidepressant agents.Bioorg. Med. Chem. Lett.20112171937194110.1016/j.bmcl.2011.02.040 21377878
    [Google Scholar]
  15. BasanagoudaM. JambagiV.B. BarigidadN.N. LaxmeshwarS.S. DevaruV. Narayanachar, Synthesis, structure-activity relationship of iodinated-4-aryloxymethyl-coumarins as potential anti-cancer and anti-mycobacterial agents.Eur. J. Med. Chem.20147422523310.1016/j.ejmech.2013.12.061 24463645
    [Google Scholar]
  16. ManvarA. BavishiA. RadadiyaA. PatelJ. VoraV. DodiaN. RawalK. ShahA. Diversity oriented design of various hydrazides and their in vitro evaluation against Mycobacterium tuberculosis H37Rv strains.Bioorg. Med. Chem. Lett.201121164728473110.1016/j.bmcl.2011.06.074 21752642
    [Google Scholar]
  17. MamidalaS. PeddiS.R. AravilliR.K. JillojuP.C. MangaV. VedulaR.R. Microwave irradiated one pot, three component synthesis of a new series of hybrid coumarin based thiazoles: Antibacterial evaluation and molecular docking studies.J. Mol. Struct.2021122512911410.1016/j.molstruc.2020.129114
    [Google Scholar]
  18. FakhryM.M. MattarA.A. AlsulaimanyM. Al-OlayanE.M. Al-RashoodS.T. Abdel-AzizH.A. New Thiazolyl-Pyrazoline derivatives as potential dual EGFR/HER2 inhibitors: Design, synthesis, anticancer activity evaluation and in silico study.Molecules20232821745510.3390/molecules28217455 37959874
    [Google Scholar]
  19. AlharbiA. QurbanJ. AbualnajaM.M. AbumelhaH.M. SaadF.A. El-MetwalyN.M. El-MetwalyN.M. Molecular modeling and docking studies of new antioxidant pyrazole-thiazole hybrids.J. Mol. Struct.2022126713358210.1016/j.molstruc.2022.133582
    [Google Scholar]
  20. PalabindelaR. GudaR. RameshG. BodapatiR. NukalaS.K. MyadaraveniP. RaviG. KasulaM. Curcumin based pyrazole-thiazole hybrids as antiproliferative agents: Synthesis, pharmacokinetic, photophysical properties, and docking studies.J. Mol. Struct.2023127513463310.1016/j.molstruc.2022.134633
    [Google Scholar]
  21. GondruR. SirishaK. RajS. GundaS.K. KumarC.G. PasupuletiM. BavantulaR. Design, synthesis, in vitro evaluation and docking studies of pyrazole‐thiazole hybrids as antimicrobial and antibiofilm agents.ChemistrySelect20183288270827610.1002/slct.201801391
    [Google Scholar]
  22. YuB. ZhouS. CaoL. HaoZ. YangD. GuoX. ZhangN. BakulevV.A. FanZ. Design, synthesis, and evaluation of the antifungal activity of novel pyrazole-thiazole carboxamides as succinate dehydrogenase inhibitors.J. Agric. Food Chem.202068277093710210.1021/acs.jafc.0c00062 32530619
    [Google Scholar]
  23. ChowdhuryM.A. AbdellatifK.R.A. DongY. DasD. SureshM.R. KnausE.E. Synthesis of celecoxib analogues possessing a N-difluoromethyl-1,2-dihydropyrid-2-one 5-lipoxygenase pharmacophore: Biological evaluation as dual inhibitors of cyclooxygenases and 5-lipoxygenase with anti-inflammatory activity.J. Med. Chem.20095261525152910.1021/jm8015188 19296694
    [Google Scholar]
  24. XuZ. GaoC. RenQ.C. SongX.F. FengL.S. LvZ.S. Recent advances of pyrazole-containing derivatives as anti-tubercular agents.Eur. J. Med. Chem.201713942944010.1016/j.ejmech.2017.07.059 28818767
    [Google Scholar]
  25. RashadA.E. HegabM.I. Abdel-MegeidR.E. FathallaN. Abdel-MegeidF.M.E. Synthesis and anti-HSV-1 evaluation of some pyrazoles and fused pyrazolopyrimidines.Eur. J. Med. Chem.20094483285329210.1016/j.ejmech.2009.02.012 19285757
    [Google Scholar]
  26. VaarlaK. KesharwaniR.K. SantoshK. VedulaR.R. KotamrajuS. ToopuraniM.K. Synthesis, biological activity evaluation and molecular docking studies of novel coumarin substituted thiazolyl-3-aryl-pyrazole-4-carbaldehydes.Bioorg. Med. Chem. Lett.201525245797580310.1016/j.bmcl.2015.10.042 26542964
    [Google Scholar]
  27. Abdel-AziemA. BaaiuB.S. ElbazzarA.W. ElabbarF. A facile synthesis of some novel thiazoles, arylazothiazoles, and pyrazole linked to thiazolyl coumarin as antibacterial agents.Synth. Commun.202050162522253010.1080/00397911.2020.1782431
    [Google Scholar]
  28. LiY. GengJ. LiuY. YuS. ZhaoG. Thiadiazole-a promising structure in medicinal chemistry.ChemMedChem201381274110.1002/cmdc.201200355 23208773
    [Google Scholar]
  29. JainA.K. SharmaS. VaidyaA. RavichandranV. AgrawalR.K. 1,3,4-thiadiazole and its derivatives: a review on recent progress in biological activities.Chem. Biol. Drug Des.201381555757610.1111/cbdd.12125 23452185
    [Google Scholar]
  30. AsifM. Chemistry, synthesis and progress report on biological activities of thiadiazole compounds - A review.Mediterr. J. Chem.20165556858810.13171/mjc55/01606241121/asif
    [Google Scholar]
  31. JanowskaS. PanethA. WujecM. Cytotoxic properties of 1,3,4-thiadiazole derivatives-A review.Molecules20202518430910.3390/molecules25184309 32962192
    [Google Scholar]
  32. BoströmJ. HognerA. LlinàsA. WellnerE. PlowrightA.T. Oxadiazoles in medicinal chemistry.J. Med. Chem.20125551817183010.1021/jm2013248 22185670
    [Google Scholar]
  33. DatarP.A. DeokuleT.A. Design and synthesis of thiadiazole derivatives as antidiabetic agents.Med. Chem.20144390399
    [Google Scholar]
  34. SidwellR.W. RobinsR.K. HillyardI.W. Ribavirin: An antiviral agent.Pharmacol. Ther.19796112314610.1016/0163‑7258(79)90058‑5 390559
    [Google Scholar]
  35. De MonteC. CarradoriS. SecciD. D’AscenzioM. GuglielmiP. MollicaA. MorroneS. ScarpaS. AglianòA.M. GiantulliS. SilvestriI. Synthesis and pharmacological screening of a large library of 1,3,4-thiadiazolines as innovative therapeutic tools for the treatment of prostate cancer and melanoma.Eur. J. Med. Chem.201510524526210.1016/j.ejmech.2015.10.023 26498571
    [Google Scholar]
  36. MullicanM.D. WilsonM.W. ConnerD.T. KostlanC.R. SchrierD.J. DyerR.D. Design of 5-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3,4-thiadiazoles, -1,3,4-oxadiazoles, and -1,2,4-triazoles as orally active, nonulcerogenic antiinflammatory agents.J. Med. Chem.19933681090109910.1021/jm00060a017 8478906
    [Google Scholar]
  37. FoksH. Pancechowska-KsepkoD. GobisK. Synthesis and characterization of novel N‐alkylamine‐ and N‐cycloalkylamine‐derived 2‐benzoyl‐N‐aminohydrazinecarbothioamides, 1,3,4‐thiadiazoles and 1,2,4‐triazole‐5(4H)thiones.J. Heterocycl. Chem.201451250751210.1002/jhet.1640
    [Google Scholar]
  38. SerbanG. Synthetic compounds with 2-amino-1,3,4-thiadiazole moiety against viral infections.Molecules202025494210.3390/molecules25040942 32093125
    [Google Scholar]
  39. ShivakumaraN. Murali KrishnaP. Synthesis, spectral characterization and DNA interactions of 5-(4-substituted phenyl)-1,3,4-thiadiazol-2-amine scaffolds.J. Mol. Struct.2020119912699910.1016/j.molstruc.2019.126999
    [Google Scholar]
  40. SinghA.K. MishraG. JyotiK. Review on biological activities of 1,3,4-thiadiazole derivatives.J. Appl. Pharm. Sci.201114449
    [Google Scholar]
  41. BanerjeeB. Recent developments on ultrasound assisted catalyst-free organic synthesis.Ultrason. Sonochem.201735Pt A11410.1016/j.ultsonch.2016.09.02327771266
    [Google Scholar]
  42. BanerjeeB. Recent developments on ultrasound-assisted synthesis of bioactive N-heterocycles at ambient temperature.Aust. J. Chem.201770887288810.1071/CH17080
    [Google Scholar]
  43. MamidalaS. AravilliR.K. RameshG. KhajavaliS. ChedupakaR. MangaV. VedulaR.R. A facile one-pot, three-component synthesis of a new series of thiazolyl pyrazole carbaldehydes: In vitro anticancer evaluation, in silico ADME/T, and molecular docking studies.J. Mol. Struct.2021123613035610.1016/j.molstruc.2021.130356
    [Google Scholar]
  44. ZhangQ.Q. JinR.C. The application of low-intensity ultrasound irradiation in biological wastewater treatment: A review.Crit. Rev. Environ. Sci. Technol.201545242728276110.1080/10643389.2015.1046772
    [Google Scholar]
  45. SalmanA.S. MahmoudN.A. MohamedM.A. Abdel-AziemA. ElsisiD.M. Synthesis, characterization and in vitro cytotoxic evaluation of some novel heterocyclic compounds bearing the indole ring.Am. J. Org. Chem.201663953
    [Google Scholar]
  46. ElokhinaV.N. KarnaukhovaR.V. NakhmanovichA.S. LarinaL.I. LopyrevV.A. Reaction of thiosemicarbazones from heterocyclic series with acetic anhydride.Russ. J. Org. Chem.200238229729910.1023/A:1015550708981
    [Google Scholar]
  47. KubotaS. UedaY. FujikaneK. ToyookaK. ShibuyaM. Synthesis of 4-acyl-2-(acylamino)-.DELTA.2-1,3,4-thiadiazolines and 4-acyl-2-amino-.DELTA.2-1,3,4-thiadiazolines by acylation of thiosemicarbazones.J. Org. Chem.19804581473147710.1021/jo01296a025
    [Google Scholar]
  48. SharmaB. VermaA. PrajapatiS. SharmaU.K. Synthetic methods, chemistry, and the anticonvulsant activity of thiadiazoles.Int. J. Med. Chem.2013201311610.1155/2013/348948 25405032
    [Google Scholar]
  49. HamamaW.S. GoudaM.A. Abd El-WahabM.H. ZoorobH.H. Recent advances in the chemistry and synthetic uses of amino‐1,3,4‐thiadiazoles.J. Heterocycl. Chem.20145161558158110.1002/jhet.1872
    [Google Scholar]
  50. DongJ. PeiQ. WangP. MaQ. HuW. Optimized POCl3-assisted synthesis of 2-amino-1,3,4-thiadiazole/1,3,4-oxadiazole derivatives as anti-influenza agents.Arab. J. Chem.2022154103712
    [Google Scholar]
  51. SchatzJ. GogićK. BenkertT. 1,3,4-Thiadiazoles.Compreh. Heterocyc. Chem.2022IV407447
    [Google Scholar]
  52. NahiR.J. ImranN.H. Synthesis, characterization and thermal stability study of new heterocyclic compounds containing 1,2,3-triazole and 1,3,4-thiadiazole rings.Orient. J. Chem.20193523424010.13005/ojc/350128
    [Google Scholar]
  53. MahmoudA.M. Al-AbdA.M. LightfootD.A. El-ShemyH.A. Anti-cancer characteristics of mevinolin against three different solid tumor cell lines was not solely p53-dependent.J. Enzyme Inhib. Med. Chem.201227567367910.3109/14756366.2011.607446 21883038
    [Google Scholar]
  54. BashmailH.A. AlamoudiA.A. NoorwaliA. HegazyG.A. AJabnoorG. ChoudhryH. Al-AbdA.M. Thymoquinone synergizes gemcitabine anti-breast cancer activity via modulating its apoptotic and autophagic activities.Sci. Rep.2018811167410.1038/s41598‑018‑30046‑z 30076320
    [Google Scholar]
  55. NunezR. DNA measurement and cell cycle analysis by flow cytometry.Curr. Issues Mol. Biol.2001336770 11488413
    [Google Scholar]
  56. PhilipS. KumarasiriM. TeoT. YuM. WangS. Cyclin-dependent kinase 8: A new hope in targeted cancer therapy?Miniperspective. J. Med. Chem.201861125073509210.1021/acs.jmedchem.7b00901 29266937
    [Google Scholar]
  57. MorrisG.M. GoodsellD.S. HallidayR.S. HueyR. HartW.E. BelewR.K. OlsonA.J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function.J. Comput. Chem.199819141639166210.1002/(SICI)1096‑987X(19981115)19:14<1639:AID‑JCC10>3.0.CO;2‑B
    [Google Scholar]
  58. DeLanoW.L. PyMOL: An Open-Source Molecular Graphics Tool.Available from: https://legacy.ccp4.ac.uk/newsletters/newsletter40/11_ pymol.pdf
  59. Discovery studio.Available from: https://discover.3ds.com/discovery-studio-visualizer-download
  60. 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]
  61. OthmanI.M.M. AlamshanyZ.M. TashkandiN.Y. Gad-ElkareemM.A.M. Abd El-KarimS.S. NossierE.S. Synthesis and biological evaluation of new derivatives of thieno-thiazole and dihydrothiazolo-thiazole scaffolds integrated with a pyrazoline nucleus as anticancer and multi-targeting kinase inhibitors.RSC Advances202112156157710.1039/D1RA08055E 35424523
    [Google Scholar]
  62. GuerraouiA. GoudjilM. DiremA. GuerraouiA. Şengünİ.Y. ParlakC. DjedouaniA. ChelazziL. MontiF. LunedeiE. BoumazaA. A rhodanine derivative as a potential antibacterial and anticancer agent: Crystal structure, spectral characterization, DFT calculations, Hirshfeld surface analysis, in silico molecular docking and ADMET studies.J. Mol. Struct.2023128013502510.1016/j.molstruc.2023.135025
    [Google Scholar]
/content/journals/coc/10.2174/0113852728326529240830101731
Loading
/content/journals/coc/10.2174/0113852728326529240830101731
Loading

Data & Media loading...

Supplements

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


  • Article Type:
    Research Article
Keyword(s): ADMET profile; anticancer; Coumarin; molecular docking; pyrazole; thiadiazole; thiazole; ultrasound
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