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
JOURNAL OF MOLECULAR STRUCTURE, vol.1312, 2024 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 1312
- Publication Date: 2024
- Doi Number: 10.1016/j.molstruc.2024.138477
- Journal Name: JOURNAL OF MOLECULAR STRUCTURE
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, Chimica, Compendex, INSPEC
- Hacettepe University Affiliated: Yes
Abstract
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.