Chemical Review and Letters

Design, synthesis, molecular docking, and preliminary pharmacological evaluation of new thioimidazole -4-one derivatives

Document Type : Research Article

Authors

Noor Mohammed Mousa 1
Abdull Jabar Attia 2
Karima Fadhil Ali 1

1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mustansiriyah University, Baghdad, Iraq.

2 College of Sciences, Mustansiriyah University, Baghdad, Iraq.

https://doi.org/10.22034/crl.2025.501629.1526
Abstract
This study investigates the synthesis, cytotoxic activity, and DNA-damaging potential of novel compounds targeting asthma-related pathways, particularly the A2A adenosine receptor. Eight synthesized compounds (4a-d, 7a-d) were evaluated for their cytotoxicity using the MTT assay on RAW 264.7 cells, with Theophylline as a standard. Compound (7d) demonstrated the least cytotoxic effect, while (4a-d) exhibited strong inhibitory activity with low IC₅₀ values. DNA damage was assessed using the comet assay on peripheral blood mononuclear cells (PBMCs). Hydrogen peroxide (H₂O₂) was used as a positive control, producing significant DNA fragmentation, while (7d) showed minimal DNA migration, indicating a potentially safer genotoxic profile. Binding interactions with the A2A receptor were explored through molecular docking, revealing hydrogen bonding and key short contacts with specific receptor residues. Compounds (4b) and (7a) achieved high PLP fitness scores, underscoring their strong receptor affinity. These findings highlight the potential of these compounds for further exploration as asthma therapeutics with selective targeting capabilities and minimized cytotoxic and genotoxic effects. Novel compounds reduced LPS-induced cytokine levels, showing potential anti-inflammatory effects, particularly for TNF-α, IL-6, and IL-1 modulation.

Graphical Abstract

Design, synthesis, molecular docking, and preliminary pharmacological evaluation of new thioimidazole -4-one derivatives

Keywords

Imidazolidine derivatives
A2A adenosine receptor
Molecular docking
MTT assay
Comet assay
DNA damage
Cytokine measurement
LPS-induced inflammation

Subjects

Chemical Review and Letters
Volume 8, Issue 6 - Serial Number 6
November and December 2025
Pages 1278-1294

  • Receive Date 23 January 2025
  • Revise Date 24 February 2025
  • Accept Date 26 February 2025

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