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

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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.