Molecular modeling and docking of new 2-acetamidothiazole-based compounds as antioxidant agents

Abstract

The highly versatile, 2-chloroacetamido-5-(4-chlorophenylazo)thiazole (2) was synthesized and used as a precursor for the production of five 2-(2-substitutedacetamido)thiazole compounds by its reaction with different types of nucleophiles such as piperidine, morpholine, 2-mercaptobenzothiazole, 4,6-dimethyl-2-mercaptonicotinonitrile and 6-amino-2-mercapto pyrimidin-4-ol. DFT/B3LYP calculations of the isolated derivatives showed that their HOMO consisted mainly of the non-bonding lone pairs of heteroatoms while LUMO were π*-orbitals of the 2-acetamido-5-(4-chlorophenylazo)thiazole moiety. Despite the close energy gap values (ΔEH-L) of the investigated compounds, the data showed that thiazole-pyrimidine derivative 8 has the highest energy gap while the thiazole-piperidine derivative 3a was the lowest. The DPPH antioxidant activity examination results, in comparison to BHT (Butylated hydroxytoluene) and Ascorbic acid as controls, showed that sulfide compounds 4, 6, and 8 had more respectable inhibitions (IC50 = 24.17–32.26 µg/mL). Moreover, the molecular docking studies of the synthesized derivatives using protein (PDB Code-2Y9X) indicated that the sulfide compounds 4, 6, and 8 had a superior binding score, −6.3934, −6.5735, and −7.2835 kcal/mol, respectively. The docking results were satisfactory, and they matched the antioxidant investigation's conclusions.

Keywords

• 2-Chloroacetamidothiazole
• Morpholine
• Sulfide
• DFT calculations
• Antioxidant
• Binding score