engleski

Preparation and in vitro screening of novel heterocyclic glycoconjugate cholinesterase inhibitors

Compounds containing a heterocyclic moiety attached to a carbohydrate system are important biologicaly active compounds. Pyridinium, imidazolium and benzimidazolium derivatives, among others, have been used in natural product chemistry and organic synthesis. Furthermore, they exibit a wide variety of biological activities. It is well established that the cholinesterases (ChE), particularly butyrylcholinesterase (BChE), are associated with te patogenesis and progression of Alzheimer's and Parkinson's disease.1 Cholinesterase inhibitors (ChEI) have been widely recognized as an effective palliative treatment for Alzheimer's and Parkinson's disease, preventing the breakdown of neurotrasmitter acetylcholine (ACh) by inhibiting ChE in the brain regions relevant for the above mentioned diseases.1 Many heterocyclic glycoconjugates have received a great deal of attention in this field of research. A series of novel heterocyclic β-D-gluco-, β-D- galacto- and α-D-mannopyranoside derivatives was synthesised as potential BChE inhibitors. Synthesis of target molecules was conducted in four steps: protection of sugar hydroxyl groups by peracetylation, O-glycosylation of the anomeric C-atom with 2-bromoethanol leading to the introduction of two C-atoms spacer followed by condensation with pyridine, imidazole and benzimidazole derivatives and the final removal of acetyls as protecting groups. All compounds were prepared in good yields and were characterized by standard analytical methods (1D NMR, IR, MS) and optical rotation measurements. Inhibitory properties of all synthesized compounds towards BChE were studied by applying Ellman's method.2, 3 Kinetic parameters (Km, Vm) and the inhibition constant (Ki) were determined.

gycoconjugate, heterocycle, butyrylcholinesterase, inhibitors

Rad u okviru projekta Hrvatska zaklade za znanost (PEPTGLYCOSAR, IP 2014-09-7899)