Synthesis, X-ray, spectroscopic characterizations, DFT calculations, Hirschfeld surface analyses, molecular docking, and molecular dynamic simulations of some 1,4-benzothiazine-1,1-dioxide derivatives as human kinase CK2 inhibitors

Irrou E., Elmachkouri Y. A., Varadharajan V., El Monfalouti H., Anouar E. H., HÖKELEK T., ...Daha Fazla

JOURNAL OF MOLECULAR STRUCTURE, cilt.1312, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1312
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1016/j.molstruc.2024.138477
  • Dergi Adı: JOURNAL OF MOLECULAR STRUCTURE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, Chimica, Compendex, INSPEC
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Several derivatives (4a-d - 5a-d) based on 1,4-benzothiazine-1,1-dioxide were synthesized in this study. The process began by preparing 1,4-benzothiazin-3-one 2 from 2-aminothiophenol 1 and 2-chloroacetic acid under alkaline conditions in water. Compound 2 was then oxidized using potassium permanganate to yield 1,4-benzothiazin-3-one-1,1-dioxide 3, which was used to undergo Knoevenagel condensation with various aromatic aldehydes in dimethylformamide with sodium methoxide under different conditions. Bis 3-oxo-1,4-benzothiazine1,1-dioxide derivatives 4a-d were obtained at room temperature while heating the reaction mixture produced 2benzyl-1,4-benzothiazine dioxide compounds 5a-d. The structural characterization was performed using spectroscopic techniques, and 4c and 5a-5d were further confirmed by single-crystal X-ray diffraction (XRD) analysis. Moreover, theoretical calculations using the DFT method and Hirshfeld surface analysis showed good agreement with experimental data. Lastly, molecular docking studies revealed that 4c, 5a-5d have a binding affinity with Human Kinase CK2, with 4c exhibiting the highest binding affinity. Molecular dynamics simulation of the CK24c complex indicated stable interaction, suggesting potential therapeutic use against various diseases.