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

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, 2mercaptobenzothiazole, 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 p*-orbitals of the 2-acetamido-5-(4-chlorophenylazo)thiazole moiety. Despite the close energy gap values (delta EH-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 = 2 4.17-32.26 mu g/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.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

The highly versatile precursor, 2-chloroacetamido-5-(4-chlorophenylazo)thiazole, was successfully synthesized and used for the production of five 2-(2-substitutedacetamido)thiazole compounds through different nucleophilic reactions. The derivatives showed similar energy gap values, but sulfide compounds 4, 6, and 8 exhibited notable inhibit ions of DPPH antioxidant activity and strong binding abilities according to molecular docking studies.