Physical and chemical properties comparison of fungal and crustaceous chitosan

Abstract

A series of ester derivatives of annulated tetrahydroazocines, namely 2,3,6,11-tetrahydro-1H-azocino[4,5-b]indoles (5-10), 2,3,6,7-tetrahydro-1H-azocino[5,4-b] indoles (11-14), and 4,7,8,9-tetrahydro-1H-pyrrolo[2,3-d]azocines (15-18), synthesized through an efficient 6 → 8 membered ring expansion procedure, were investigated for their acetylcholinesterase (AChE) inhibitory activities. Most of the compounds acted as AChE inhibitors in vitro, with IC 50 values ranging from 5 to 40 μM. The most potent compounds 11 and 15, both as racemic mixtures, proved selective toward AChE, exhibiting selectivity ratios versus butyrylcholinesterase (BuChE) of ca. 15 and more than 20, respectively. Structure-activity studies highlighted, among other factors, lipophilicity as a property modulating the AChE inhibition potency, as shown by a reasonable parabolic correlation between pIC 50 and experimental 1-octanol/water partition coefficient (log P), which described the prevailing behavior of the examined compounds (r 2 = 0.665). Molecular docking simulations using the X-ray crystal structure of AChE from Torpedo californica suggested possible binding modes of the tetrahydroazocine ester derivatives 11 and 15. © 2006.