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

摘要

The 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, H-1, C-13 NMR and mass spectral data. The title compounds were tested for their potential to inhibit the activity of enzymes alpha-glucosidase and alpha-amylase. It was found that most of the derivatives showed good enzyme inhibitory activity while compound 3j exhibited excellent activity with IC50 values 0.051 and 0.0082 mM for alpha-glucosidase and alpha-amylase, respectively. The presence of 3,5-di-NO2 functional groups at aromatic ring in compound 3j play important role in enzyme inhibitory activity. The enzyme inhibitory kinetic analysis of the most potent derivative 3j revealed that it is a mixed type inhibitor of alpha-glucosidase with Ki and Ki' values 0.0339 and 0.1562 mM, respectively. It was further investigated that compound 3j formed reversible enzyme inhibitor complex with alpha-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 compound 3j may act as a lead structure for the development of most potent alpha-glucosidase inhibitors.