New thiazole and thiazole-chromene hybrids possessing morpholine units: Piperazine-mediated one-pot synthesis of potential acetylcholinesterase inhibitors

Abstract

In the current study, new morpholine-linked thiazoles were prepared by the reaction of salicylaldehyde derivative, thiosemicarbazide, and α-bromoketones. To mediate the previous three-component reaction, the reaction was conducted using two equiv. of piperazine in dioxane at reflux for 5 h. Using the prior protocol, two series of thiazoles, linked to arene or chromene units, were prepared in good to excellent yields. The new thiazoles were examined as potential inhibitors of acetylcholinesterase at a concentration of 50 µM. When compared to donepezil (inhibition percentage of 92.8%), hybrids 11b and 11c, linked to 6-chloro or 6-bromochromen-3-yl units, gave the best inhibition percentages of 72.3 and 71.5%, respectively. Furthermore, when tested at a concentration of 25 µg/mL, the same hybrids demonstrated the highest DPPH antioxidant activity, with inhibition percentages of 84.1 and 83.2%, respectively, when compared to ascorbic acid (inhibition percentage of 89.5%).

Graphical Abstract

Keywords:

• Acetylcholinesterase inhibitory activity
• Alzheimer’s disease
• chromenes
• DPPH antioxidant activity
• Hantzsch thiazole synthesis