Piperazine-based Semicarbazone Derivatives as Potent Urease Inhibitors: Design, Synthesis, and Bioactivity Screening

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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. Objective: This study aimed to synthesize and evaluate the bioactivity of a series of semicarbazone derivatives. Methods: A series of piperazine-based semicarbazone derivatives 5a-o were synthesized and isolated, and their structures were elucidated by1H-NMR and13C-NMR spectroscopic techniques besides MS and elemental analysis. The urease inhibition activity of these compounds was evaluated using the standard urease enzyme inhibition kit. An MTT assay was performed on two different cell lines (NIH-3T3 and MCF-7) to investigate the cytotoxicity profile. Results: All semicarbazone 5a-o exhibited higher urease inhibition activity (3.95-6.62 µM) than the reference standards thiourea and hydroxyurea (IC50: 22 and 100 µM, respectively). Derivatives 5m and 5o exhibited the best activity with the IC50 values of 3.95 and 4.05 µM, respectively. Investigating the cytotoxicity profile of the target compound showed that all compounds 5a-o have IC50 values higher than 50 µM for both tested cell lines. Conclusion: The results showed that semicarbazone derivatives could be highly effective as urease inhibitors.

Original languageEnglish
Pages (from-to)1111-1120
Number of pages10
JournalLetters in Drug Design and Discovery
Volume19
Issue number12
DOIs
Publication statusPublished - Dec 2022
Externally publishedYes

Keywords

  • Enzyme inhibitors
  • Piperazine
  • Rational drug design
  • Semicarbazone
  • Synthesis
  • Urease

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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