Highly selective inhibition of butyrylcholinesterase by a novel melatonin–tacrine heterodimers |
| |
Authors: | Anna Zawadzka Iwona Łozińska Zuzanna Molęda Mirosława Panasiewicz Zbigniew Czarnocki |
| |
Institution: | 1. Faculty of Chemistry, University of Warsaw, , Warsaw, Poland;2. Department of Biochemistry, Medical Center of Postgraduate Education, , Warsaw, Poland |
| |
Abstract: | Novel inhibitors of cholinesterases, especially butyrylcholinesterase (BuChE), were obtained by coupling melatonin–tacrine heterodimers via the carbamate bond. Compounds 14a‐i possessed potent cholinesterase inhibitory activity (with IC50 values as low as 1.18 nm for acetylcholinesterase (AChE) and 0.24 nm for butyrylcholinesterase (BuChE)). These heterodimers exhibit selectivity toward BuChE, being from 4‐ to 256‐fold more active toward BuChE than AChE, but still acting as better AChE inhibitors than tacrine 4 . |
| |
Keywords: | Alzheimer's disease cholinesterases inhibitors hybrid drugs |
|
|