New piperazine-based bis(thieno[2,3-b]pyridine) and bis(pyrazolo[3,4-b]pyridine) hybrids linked to benzofuran units: Synthesis and in vitro screening of potential acetylcholinesterase inhibitors

Abstract

Two series of piperazine-based bis(thieno[2,3-b]pyridines) and bis(pyrazolo[3,4-b]pyridines) were prepared, in good yields, utilizing the appropriate bis(pyridinethione). The first series was obtained by reacting the previous synthon with different α-halogenated reagents, whereas the second series was produced by reacting the synthon with various hydrazonyl chlorides, and then cyclizing the resulting bis(hydrazonothioates). At 50 and 100 µM concentrations, the two series were screened as potential acetylcholinesterase inhibitors. The reference donepezil had inhibition percentages of 90.7 and 93.5 at the tested concentrations. Generally, bis(thieno[2,3-b]pyridine) series was found to be more effective than the other series of bis(pyrazolo[3,4-b]pyridine). Bis(thieno[2,3-b]pyridine-2-carbonitrile) inhibited acetylcholinesterase the best, with inhibition percentages of 55.2 and 88.4 at 50 and 100 µM concentrations, respectively. Furthermore, when tested at a concentration of 25 µg/mL, the prior hybrid demonstrated the best DPPH antioxidant activity, with an inhibition percentage of 81.5 when compared to the reference ascorbic acid (inhibition percentage of 88.7).

Graphical Abstract

Keywords:

• Acetylcholinesterase inhibitors
• Alzheimer’s disease
• Piperazine-based hybrids
• Pyrazolo[3,4-b]pyridines
• Thieno[2,3-b]pyridines