Thiosemicarbazone Derivatives Act as Potent Urease Inhibitors; Synthesis, Bioactivity Screening and Molecular Docking Study. Issue 23 (14th June 2022) - Moghadam, Ebrahim Saeedian
Abstract: 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 ( 1 H‐NMR, 13 C‐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. Abstract : Herein, fourteen different thiosemicarbazone derivatives 5 a–n were designed, synthesized and screened as urease inhibitors. All synthesized compounds showed interesting urease inhibitory effect with the IC50 values of 4.08‐11.31 μM. In parallel, cytotoxicity of all 5 a–n were evaluated using MTT method on two different cell lines which exhibited IC50 values higher than 50 μM. Current synthesized series, could be considered as an interesting scaffold to find highly potent and safe urease inhibitor.