فهرست نشریات علمی دسترسی آزاد ایران

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.