Novel substituted benzothiazole and Imidazo[2,1-b][1,3,4]Thiadiazole derivatives: Synthesis, characterization, molecular docking study, and investigation of their in vitro antileishmanial and antibacterial activities

Abstract

In this study, we synthesized new imidazo[2,1-b][1,3,4]thiadiazole derivatives containing benzothiazole group. To this end, we firstly obtained the benzo[d]thiazol-2-ylthio/oxy acetonitrile compounds (3a,b), the starting materials, in high yields (82% and 87%, respectively). Then, we synthesized the 2-amino-1, 3,4-thiadiazole derivatives (4a,b) from the reaction of these nitrile derivatives (3a,b) with thiosemicarbazide in trifluoroacetic acid (TFA) (in yields of 83% and 84%). Finally, we synthesized the imidazo[2,1-b][1,3,4]thiadiazole derivatives (5-24) containing benzothiazole group, which are the target compounds, from reactions of 2-amino-1,3,4-thiadiazole derivatives (4a,b) with phenacyl bromide derivatives (in yields of 53%–73%).All of the compounds synthesized were characterized with 1H NMR, 13C NMR, FT-IR, elemental analysis, and mass spectroscopy.Antileishmanial and antibacterial activity tests were applied to the compounds synthesized in the study. It was observed that compound 8 had the highest antileishmanial activity (MIC = 10 000 μg/mL). Also, compounds 7 and 17 were found to be effective at the highest concentration studied (MIC = 20 000 μg/mL). In terms of antibacterial activity, compounds 4b and 7 were found to be the most effective compounds against Escherichia coli (MIC = 625 μg/mL).Theoretical calculations were performed to support the experimental results. To this end, we performed Molecular Docking studies to determine whether or not the compounds (4a, 4b, 7 and 13) optimized with Gaussian09 using the DFT/B3LYP/6-31G(d,p) theory, which is a quantum chemical calculation, could be an inhibitor agent for the 2eg7 Escherichia coli protein structure. Also, we investigated the relationship between the calculated HOMO values of these four ligands and docking studies.