engleski

4-aminoquinolines, a privileged pharmacophore - from antimalarials to inhibition of cholinesterase

Quinoline heterocycle is one of the few privileged scaffold that express a broad spectrum of biological activity. 4-Aminoquinolines (4-AQ), an important sub-group of quinoline family, was primarily boosted in the middle of the 20th century as replacement of quinine, and were the firstline defenders for the treatment of malaria for decades. However, discover that 4-AQ based compounds exhibit wide biological activity that influenced many biochemical processes, placed this pharmacophore in the centre of drug repurposing programs. Although it is known that quinoline influenced degradation of Alzheimer β/A4 amyloid precursor protein and that inhibits human erythrocyte membrane AChE, just recently more detailed investigation of 4-AQ as potentially active agents are reported. As part of our broader research in this field, we investigate 4-AQ as reversible inhibitors of AChE and BChE. We synthesized a series of derivatives that differs in the structure of diamino alkyl- or aryl-side chain and substitution on the terminal amino group. Starting from the corresponding 4-chloroquinoline and using different alkyl- or aryl-diamines corresponding 4- aminoquinolines were obtained. Further modifications of terminal amino-group produced final derivatives that were examined as inhibitors of cholinesterase’s activity. We found that length of the side chain, conformation flexibility and substitution of aryl-group influenced the inhibitory capacity of AChE and BChE and selectivity as well. Other details will be discussed.

4-aminoquinolines ; acetylcholinesterase ; butyrylcholinesterase ; selectivity ; Alzheimer`s disease

nije evidentirano