Synthesis and enzyme inhibitory kinetics of some novel 3-(substituted benzoyl)-2-thioxoimidazolidin-4-one derivatives as α-glucosidase/α-amylase inhibitors

AbstractThe present work describes an efficient and convenient synthesis of a library of novel 3-(substituted benzoyl)-2-thioxoimidazolidin-4-ones(3a –j). The benzoyl isothiocyanates were treated with glycine in the presence of pyridine, the reactants got consumed giving a variety of thioxoimidazolidin-4-ones derivatives under mild reaction conditions. The structures of the compounds were determined by elemental analysis, FTIR,1H,13C NMR and mass spectral data. The title compounds were tested for their potential to inhibit the activity of enzymes α-glucosidase and α-amylase. It was found that most of the derivatives showed good enzyme inhibitory activity while compound3j exhibited excellent activity with IC50 values 0.051 and 0.0082  mM for α-glucosidase and α-amylase, respectively. The presence of 3,5-di-NO2 functional groups at aromatic ring in compound3j play important role in enzyme inhibitory activity. The enzyme inhibitory kinetic analysis of the most potent derivative3j revealed that it is a mixed type inhibitor of α-glucosidase withKi andKi ʹ values 0.0339 and 0.1562  mM, respectively. It was further investigated that compound3j formed reversible enzyme inhibitor complex with α-glucosidase. The cytotoxicity of all the synthesized compounds was also evaluated and results showed that none of these compounds displayed toxicity against brine shrimps. Based upon results, it is suggested that compound3j may act as a lead structure for the development of most po...
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research