Design and synthesis of tacrine–ferulic acid hybrids as multi-potent anti-Alzheimer drug candidates

Five tacrine–ferulic acid hybrids (6a–e) were designed and synthesized as multi-potent anti-Alzheimer drug candidates. All target compounds have better acetylcholinesterase inhibitory activity and comparable butyrylcholinesterase inhibitory activity in relation to tacrine. Interestingly, 6d showed a reversible and non-competitive inhibitory action for acetylcholinesterase indicating interaction with the peripheral anionic site, whereas a reversible but competitive inhibitory action for butyrylcholinesterase. The antioxidant study revealed that four target compounds have, compared to Trolox, high ability to absorb reactive oxygen species.

Graphical abstractNovel ChE inhibitory (IC50: AChE 4.4–38.6 nM; BChE 5.9–34.1 nM) and antioxidant (0.4–2.0 equiv to Trolox) tacrine–ferulic acid hybrids are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide