Discovery of benzothiazole-based thiazolidinones as potential anti-inflammatory agents: anti-inflammatory activity, soybean lipoxygenase inhibition effect and molecular docking studies

Despite the greatest achievement in the development of anti-inflammatory agents in the last two decades, the current clinical drugs suffer from a variety of complications in community settings and hospital. There is still an urgent need to design novel molecules with better safety profile and with different molecular targets from those in current clinical use. The aim of this research was to discover a series of benzothiazole-based thiazolidinones with lipoxygenase (LOX) inhibitory activity as a mechanism of anti-inflammatory action. Carrageenan-induced mouse foot paw oedema assay was carried out to determine the anti-inflammatory activity, while LOX inhibition was examined through the conversion of sodium linoleate to 13-hydroperoxylinoleic acid. Molecular docking studies were performed using AutoDock 4.2 software. The anti-inflammatory activity of the title compounds was determined in a range of 18.4%-69.57%, where compound #3 was found to be the most potent (69.57%) and also to be more active than the reference drug indomethacin (47%). Moreover, compound #3 showed the highest LOX inhibitory activity with IC50 of 13 μM being less potent to that of the reference NDGA (IC50 = 1.3 μM). Compound #3 has been identified as lead compound for further modification in an attempt to improve anti-inflammatory and LOX inhibitory activities.