New 5-Iodoisatin Preparation, Spectroscopic Characterization, Antioxidant, Urease Inhibition Activities, DFT Studies, Molecular Docking, and Molecular Dynamic Simulations

Abstract

New isatin-thiosemicarbazone compounds (<bold>1</bold>-<bold>7</bold>) were synthesized from numerous thiosemicarbazides and 5-iodoisatin with high yields and efficient methods. The compounds' structures were characterized through FT-IR, H-1 NMR, and C-13 NMR spectroscopy, supported by elemental analysis. Density functional theory (DFT) calculations were employed to investigate the structural and electronic properties of the compounds, with a discussion on their correlation to antioxidant activity. The antioxidant potential of the synthesized compounds was evaluated in vitro using the 1,1-diphenyl-2-picryl hydrazyl (DPPH.) free radical scavenging assay. These compounds exhibited IC50 values ranging from 15.36 +/- 0.03 to 22.46 +/- 0.05 mu M, with compound <bold>7</bold> demonstrating the best antioxidant activity among them. The free radical scavenging effects of the compounds, based on their IC50 values, followed the order: <bold>7</bold> > <bold>4</bold> > <bold>6</bold> > <bold>5</bold> > <bold>3</bold> > <bold>2</bold> > <bold>1</bold>. Urease inhibition of the samples and their interactions with urease were examined, and it was determined that compound <bold>2</bold> showed the best inhibition effect and interaction as 1.62 +/- 0.05 mu g/mL and - 7.70 kcal/mol, respectively. Molecular docking was used to ascertain how each molecule interacted with the active areas of the urease enzymes. In addition, molecular dynamics simulation was performed to determine the state of the complex it formed with the enzyme. The current study determined that in vivo biochemical tests of effective thiosemicarbazones could be used to evaluate useful application sectors such as the biological and pharmaceutical fields.