Synthesis, Structural, DFT studies, Biological Effectiveness, and Molecular Docking Aspects of Multitarget Novel N-(4-Phenylthiazol-2-yl)hydrazine carboxamide Hybrids as COX inhibitors, Anti-TB, and Anti-oxidant activity

We herein report, a series of N-(4-phenylthiazol-2-yl)hydrazinecarboxamide based multitarget compounds 3(a-i) were designed and synthesized. Ten compounds 2, and 3(a-i) were characterized by FTIR, NMR (H-1 and C-13), and mass analysis and subsequently, tested for their potential COX inhibitors, anti-TB, and anti-oxidant activities. The physicochemical and ADME studies for newly synthesized compounds were disclosed. The DFT calculations were taken for the selected molecules using CAM-B3LYP hybrid functional with a 6-31+g(d) all-electron basis set using the Gaussian 09 package. The compounds 3d, 3e, and 3f recognized outstanding COX-II inhibitions with IC50 values of 0.62, 0.78, and 0.72 mu M compared to standard drugs. The compounds 3d, 3e, and 3f showed outstanding anti-TB activity with a MIC value of 0.78 mu g/mL. The compound 3d, and 3f attested outstanding antioxidant activity at 10 mu g/mL with a rate of inhibition of 68.12%, and 68.85% respectively. Finally, the molecular docking studies carried out with cyclooxygenase-2 (PDB ID: 6COX), M. tuberculosis enoyl reductase (INHA) (PDB ID: 4TZK), and cytochrome c peroxidase (PDB ID: 2x08), for all the newly synthesized derivatives. Finally, selected compounds were taken for their molecular dynamic studies.