Acetylcholinesterase inhibition by tacrine analogues

• Published in: Bioorganic & medicinal chemistry letters Vol. 7; no. 20; pp. 2599 - 2602
• Main Authors: Valenti, Piero, Rampa, Angela, Bisi, Alessandra, Andrisano, Vincenza, Cavrini, Vanni, Fin, Lorena, Buriani, Alessandro, Giusti, Piero
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 21.10.1997; Elsevier
• Subjects: Biological and medical sciences; Cholinergic system; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Sulfur nitrogen heterocycle; Rat; Enzyme; Nitrogen heterocycle; Rodentia; Central nervous system; Enzyme inhibitor; Esterases; Tetracyclic compound; Acetylcholinesterase; In vitro; Carboxylic ester hydrolases; Vertebrata; Mammalia; Amine; Structure activity relation; Animal; Hydrolases; Aromatic compound; Anticholinesterase agent; Chemical synthesis; Brain (vertebrata); Oxygen nitrogen heterocycle
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(97)10025-7

Analogues of tacrine were synthesized and evaluated for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity. Compound 2a was the most potent inhibitor of AChE with a higher selectivity than tacrine for AChE over BuChE. Tacrine, on the other hand, showed the opposite behaviour with a weaker inhibitory effect on AChE than on BuChe. The compounds displayed correlated activities in isolated enzymes as well as in rat brain homogenates. Some analogues of tacrine are described. Compound 2a was the most potent inhibitor of A ChE and showed a definite preference for A ChE over BuChE with a higher selectivity than tacrine, which on the other hand showed an opposite behaviour with a less inhibitory effect on A ChE.