Medicinal Chemistry Research

, Volume 27, Issue 5, pp 1528–1537 | Cite as

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

Original Research
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Abstract

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, 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 compound 3j 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 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 α-glucosidase with Ki and Kiʹ values 0.0339 and 0.1562 mM, respectively. It was further investigated that compound 3j 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 compound 3j may act as a lead structure for the development of most potent α-glucosidase inhibitors.

Keywords

2-thioxoimidazolidin-4-ones Benzoyl isothiocyanates Enzyme inhibitory kinetics Cytotoxicity 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Rabia Qamar
    • 1
  • Aamer Saeed
    • 1
  • Maria Saeed
    • 1
  • Babar Hussain Shah
    • 1
  • Zaman Ashraf
    • 2
  • Qamar Abbas
    • 3
  • Sung Yum Seo
    • 4
  1. 1.Department of ChemistryQuaid-i-Azam UniversityIslamabadPakistan
  2. 2.Department of ChemistryAllama Iqbal Open UniversityIslamabadPakistan
  3. 3.Department of PhysiologyUniversity of SindhJamshoroPakistan
  4. 4.Department of Biology, College of Natural SciencesKongju National UniversityGongjuRepublic of Korea

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