Synthesis, Characterization and in vitro Biological Evaluation of Benzothiazole-Phenylsulfonyl Urea Hybrid Analogues as Antibacterial and Antidiabetic Agents

Abstract

The global burden of antibacterial resistance, along with the increasing prevalence of diabetes worldwide, has intensified the search for new therapeutic agents with novel chemical scaffolds that possess both antibacterial and antidiabetic potential. In this study, a series of benzothiazole-phenylsulfonyl urea derivatives (C1-C6) were synthesized and their molecular structures were confirmed by HRMS-ESI, ATR FT-IR, ¹H and ¹³C NMR spectral data. The in vitro antibacterial activity was evaluated against both susceptible and resistant bacterial strains, including Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Acinetobacter baumannii, using the broth microdilution method. All compounds exhibited low antibacterial activity (MIC > 128 µM), indicating limited potential as antibacterial agents. In addition, the same derivatives were also tested for in vitro α-glucosidase (Saccharomyces cerevisiae Type 1) inhibitory activity using an enzyme-kinetics assay. All compounds demonstrated varied degrees of inhibition (IC₅₀ = 682.25 ± 2.90 to 801.51 ± 13.46 µM) relative to voglibose (IC₅₀ = 711.04 ± 3.88 µM). Compound C3, bearing an ethoxy group at position 6 of the benzothiazole ring, showed the highest α-glucosidase inhibitory activity (IC₅₀ = 682.25 ± 2.90 µM), while compound C6, with a fluoro substitution at position 6, was the most potent within its subgroup (IC₅₀ = 744.37 ± 4.86 µM). Structure-activity relationship (SAR) analysis suggested that electron-donating substitutions at position 6 of the benzothiazole moiety enhance inhibitory potency. Overall, while these benzothiazole-phenylsulfonyl urea derivatives demonstrated only weak antibacterial activity, their α-glucosidase inhibition potential is found worthwhile for further structural optimization to develop as antidiabetic agents.