Affiliation:
1. Department of Pharmaceutical & Toxicological Chemistry Volgograd State Medical University Volgograd Russia
2. Organic Chemistry Department RUDN University Moscow Russia
3. Department of Pharmacology & Bioinformatics Volgograd State Medical University Volgograd Russia
Abstract
AbstractAfter preliminary ab initio calculations, 3‐phenacyl substituted thiazolium salts, analogs of Alagebrium, were synthesized and investigated in vitro 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 in vivo 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 in vitro tests and was able to suppress capacity of methylglyoxal to form AGEs in vivo.
Subject
Molecular Medicine,Biochemistry,Drug Discovery,Pharmacology,Organic Chemistry