Synthesis, Antimicrobial, Antioxidant and Molecular Docking Studies on Novel 6-Methoxybenzothiazole-piperazine Derivatives with Propanamide Chain.

Abstract

Infectious diseases are a major threat in the developing world and the discovery of novel antimicrobial agents remains to be crucial due to acquired resistance by the microorganisms. Additionally, various diseases can be prevented with antioxidant agents as they can eliminate the harmful effects of reactive oxygen species. In this study, it was aimed to synthesize novel compounds bearing N-(6- methoxybenzothiazol-2-yl)-3-(4-substitued piperazinyl)propanamide backbone that had antimicrobial and antioxidant activities. Mechanisms of activity were aimed to be revealed by docking studies. Antimicrobial activities were tested by agar-based disc diffusion assay, and antioxidant activities were determined by CUPRAC assay. In agar-based disc diffusion assay, the most active compounds were 2b and 2e against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Candida albicans. Compounds 2e and 2j showed promising antioxidant activity in CUPRAC assay. Docking studies were performed to optimize the interactions of compounds with DNA gyrase subunit B of S. aureus. Under the light of docking studies, a new compound with potential GyrB inhibition was designed. Antioxidant activity was also supported by docking studies on superoxide dismutase 1 enzyme in which interactions with key residues were observed. Ten novel benzothiazole-piperazine derivatives were synthesized and their antimicrobial and antioxidant activities were evaluated. Superoxide dismutase 1 enzyme was suggested to be a possible target for the antioxidant activity of the series.