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

Ebrahim Saeedian Moghadam, Abdullah Mohammed Al-Sadi, Meysam Talebi, Massoud Amanlou, Raphael Stoll, Mohsen Amini, Raid Abdel-Jalil*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 (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.

Original languageEnglish
Article numbere202200860
JournalChemistrySelect
Volume7
Issue number23
DOIs
Publication statusPublished - Jun 20 2022
Externally publishedYes

Keywords

  • Medicinal Chemistry
  • Molecular modeling
  • Synthesis
  • Thiosemicarbazone
  • Urease Inhibitors

ASJC Scopus subject areas

  • Chemistry(all)

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