Synthesis, antioxidant and anticholinesterase activities of novel coumarylthiazole derivatives

• 42 new coumarylthiazole derivatives containing urea/thiourea groups were synthesized.
• All the compounds showed inhibitory activities for AChE and BuChE.
• All the compounds exhibited high potent antioxidant activity.

A newly series of coumarylthiazole derivatives containing aryl urea/thiourea groups were synthesized and their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated. The result showed that all the synthesized compounds exhibited inhibitory activity to both cholinesterases. Among them, 1-(4-(8-methoxy-2-oxo-2H-chromen-3-yl)thiazol-2-yl)-3-(4-chlorophenyl)thiourea (f8, IC50 = 4.58 μM) was found to be the most active compound against AChE, and 1-(4-fluorophenyl)-3-(4-(6-nitro-2-oxo-2H-chromen-3-yl)thiazol-2-yl)urea (e31) exhibited the strongest inhibition against BuChE with IC50 value of 4.93 μM, which was 3.5-fold more potent than that of galantamine. The selectivity of f8 and e31 were 2.64 and 0.04, respectively. In addition, the cupric reducing antioxidant capacities (CUPRAC) and ABTS cation radical scavenging abilities of the synthesized compounds were investigated for antioxidant activity. Among them, f8, f4 and f6 (IC50 = 1.64, 1.82 and 2.69 μM, respectively) showed significantly better ABTS cation radical scavenging ability than standard quercetin (IC50 = 15.49 μM).

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