Abstract:
Hydrazones and thiazoles possess a wide spectrum of biological activities
including antimicrobial, anticonvulsant, analgesic, anti-inflammatory, antiplatelet, antitubercular and antitumour activities. Acyl hydrazones with an azomethine proton (-NHN=CH-) possess promising biological activities and existence ofthiazole bearing anti-inflammatory drugs such as Fanetizole, Meloxicam and Fentiazac prompted us to design new benzylidenehydrazinylphenylthiazoles (BHPT). BHPT compounds were
synthesised via condensation of thiosemicarbazide with aryl aldehyde, followed by cyclisation in the presence of aryl substituted 2-bromo-l-phenylethan-1-ones. The compounds were characterised using UV-VIS, FT-IR, 1H & 13C NMR, and LC-MS techniques. Anti-inflammatory activity ofthe compounds was evaluated using LPSEc (Lipopolysaccharide from E. Coli) stimulated RAW 264.7 macrophage cells. The effect of BHPT compounds on the expressions of cytokines were determined using
multi-analyte ELISA kit. The compounds significantly inhibited nitrite production in LPSEc stimulated RAW 264.7 cells with ICso (the concentration of compounds that inhibit nitrite production by 50%) values ranging between 20- 35 µM. BHPT05 is the most potent and it reversed the upregulated pro-inflammatory cytokines and downregulated anti inflammatory cytokines. The metabolic stability ofBHPT05 was determined using mouse, rat, and human liver microsomes and it found to be metabolically stable.
