Design and Biological Potential of New 6-Aryl-2-(4-(1,3-dioxoisoindolin-2-yl) phenyl)imidazo(2,1-b)1,3,4-thiadiazoles: Synthesis and Molecular Docking Studies

Abstract

By cyclocondensing 4-(1,3-dioxoisoindolin-2-yl)benzoic acid with thiosemicarbazide to form a crucial intermediate and then reacting with different substituted phenacyl chlorides, a novel series of 6-aryl-2-(4-(1,3-dioxoisoindolin-2-yl)phenyl)imidazo(2,1-b)1,3,4-thiadiazoles (3a-3e). FTIR, 1H NMR, 13C NMR and elemental analysis were used to confirm the chemical structures of these derivatives. Compound 3d demonstrated the greatest antifungal inhibition against Botryodiplodia theobromae, whereas compound 3e had the most reliable and strong antibacterial activity against both Gram-positive and Gram-negative strains, according to biological evaluation utilizing the Agar-Cup diffusion method. These experimental findings were corroborated by molecular docking investigations, which revealed significant binding affinities between -7.7 and -8.4 kcal/mol. With a docking score of -8.4 kcal/mol, compound 3a in particular showed the most stable interaction, establishing crucial connections with residues like ARG-52 and ARG-219(pdbid-1AD4). These results demonstrate the potential of an isoindoline moiety combined with the imidazo[2,1-b][1,3,4]thiadiazole scaffold as a promising template for the development of powerful antibacterial medicines.