Thiosemicarbazone Derivatives Act as Potent Urease Inhibitors; Synthesis, Bioactivity Screening and Molecular Docking Study

An enzyme called urease assists highly pathogenic bacteria in colonizing and maintaining themselves. Accordingly, inhibiting urease enzymes has been shown to be a promising strategy for preventing ureolytic bacterial infections. So, design and synthesis of potent and safe urease inhibitors converted to an interesting target for medicinal chemists. In this study, the design, synthesis, and bioactivity of fourteen thiosemicarbazone derivatives 5 a–n are described as potent urease inhibitors. A variety of spectroscopic techniques (¹H-NMR, ¹³C-NMR, MS), and elemental analysis were utilized to determine the structure of 5 a–n. Interestingly, all 5 a–n showed higher inhibitory activity (IC₅₀: 4.08 to 11.31 μM) than the standards thiourea and hydroxyurea (IC₅₀: 22 and 100 μM respectively). 5 g and 5 f exhibited the best activity with IC₅₀ values of 4.08 and 4.79 μM, respectively. Molecular docking was also used to reveal the potential interactions between the enzyme‘s active site and the most active compound. An MTT assay was conducted on two different cell lines to investigate the cytotoxic effect of the tested compounds. all 5 a–n have IC₅₀ values above 50 μM on both tested cell lines. In conclusion, current reported compounds are potent and safe enough to continue further bioassays to find a new drug candidate.