Synthesis and antiglycation activity of 3-phenacyl substituted thiazolium salts, new analogs of Alagebrium.

Abstract

After preliminary abinitio calculations, 3-phenacyl substituted thiazolium salts, analogs of Alagebrium, were synthesized and investigated invitro as glycation reaction inhibitors. The most part of investigations focused on the potential of the title compounds to attenuate the formation of fluorescent AGEs as well on their ability to disrupt the cross-linking formation among glycated proteins. Additionally, the capability of thiazolium salts to deglycate in the reaction of early glycation products with nitroblue tetrazolium was determined. Cytotoxicological properties of the title compounds were evaluated using LDH and MTT assays. The leader compound (3-[2-(biphenyl-4-yl)-2-oxoethyl]-1,3-thiazol-3-ium bromide) in a 50 mg/kg dose (p.o. 14 days) was further tested within an invivo carbonyl stress model (rats, methylglyoxal 86.25 mg/kg/d, i.p., 14 days). As a result, the leader-molecule revealed a high effectiveness against all three examined mechanisms of glycation reaction inhibition in invitro tests and was able to suppress capacity of methylglyoxal to form AGEs invivo.