Synthesis, characterization and computational studies of a series of the thiazole-thiazolidinone hybrids

A multi-step synthetic procedure yielded novel polycyclic thiazole-thiazolidinone hybrids 3-(4-(4-4-chlorobenzyloxyphenyl)thiazol-2-yl)-2-(para-nitrophenyl)thiazolidin-4-one (4a), 3-(4-(4-4-chlorobenzyloxyphenyl) thiazol-2-yl)-2-(para-bromophenyl)thiazolidin-4-one (4b), 3-(4-(4-4-chlorobenzyloxyphenyl)thiazol-2-yl)-2(para-methoxyphenyl)thiazolidin-4-one (4c), 3-(4-(4-4-chlorobenzyloxyphenyl)thiazol-2-yl)-2-(ortho-fluorophenyl)thiazolidin-4-one (4d) and 3-(4-(4-4-chlorobenzyloxyphenyl)thiazol-2-yl)-2-(meta-nitrophenyl)thiazolidin-4-one (4e). The DFT/B3LYP/6-31+G(d,p) based calculations in water were applied to study 4a-e and their corresponding protonated forms [4a-e + H]+. The cationic forms were considered as the most reliable species formed upon corrosion inhibition under acidic conditions as well as a salt-like drug form, while the aqueous medium mimics both the corrosion and the dominant component of body fluids. Compounds 4a-e as well as their protonated forms were found to be strong electrophiles. Molecules 4a-e as well as their protonated forms were probed in silico as potential inhibitors of corrosion for as a set of metals, which are the most abundant components of implants in biomedicine. The ADMET properties of compounds 4a-e as well as [4a-e + H]+ were computed. All the reported herein compounds were probed in silico as potential inhibitors of the Nonstructural protein 14 (Nsp14_N7-MTase), which is one of the most crucial proteins for the SARS-CoV-2 virus since this protein is of importance for viral replication and transcription. All the discussed compounds 4a-e as well as their protonated forms are highly active toward the applied protein, with the best binding energy found for compound 4c and the protonated form of 4b. All protein-ligand complexes are characterized by the parameters typical for a Hit, and complexes Nsp14_N7-MTase-4c and Nsp14_N7-MTase-[4b + H]+ are characterized by the parameters typical for a drug.