Design, synthesis and molecular docking studies of S- alkylated thiadiazole derivatives containing phthalimide moiety as antimicrobial agents

Abstract

Considering the incidence of infectious diseases and emergence of antibiotic-resistance bacterial and fungal strains, the discovery of new antimicrobial agents is essential. Thiadiazole as an useful pharmacophore is considered in drug discovery researches. Reported thiadiazole derivatives with antimicrobial properties indicate the importance of this scaffold as antimicrobial agent. Compounds bearing phthalimide moiety also have been identified as antimicrobial agents. The existing work was conducted to evaluate the antimicrobial property of new thiadiazole – phthalimide hybrid derivatives. Thiadiazole-phthalimide hybrid derivatives were prepared by the reaction of phthalic anhydride with amine group of various s-alkylated thiadiazole derivatives which followed by evaluation of antimicrobial properties using tube dilution technique against bacterial and fungal strains. The final molecules were docked in the active sites of Escherichia coli topoisomerase II DNA gyrase B to assay the possible interactions. Compound 3a was found to be active against Staphylococcus aureus , Escherichia coli and in particular Candida albicans with minimum inhibitory concentration values of 0.75, 0.18, 0.09 (mg/mL), respectively. None of the compounds had activity against Pseudomonas aeruginosa in studied concentrations. The highest docking score was -8.41kcal/mol for compound 3b which can confirm the experimental results.

Keywords

• Synthesis
• Thiadiazole
• Antimicrobial
• Topoisomerase
• Molecular Docking

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