A concise synthesis and evaluation of new malonamide derivatives as potential α-glucosidase inhibitors

  • Bioorg Med Chem. 2016 Apr 15;24(8):1675-82. doi: 10.1016/j.bmc.2016.02.037.
Mohammad Shahidul Islam  1 ,  Assem Barakat  2 ,  Abdullah M Al-Majid  1 ,  Hazem A Ghabbour  3 ,  A F M Motiur Rahman  4 ,  Kulsoom Javaid  5 ,  Rehan Imad  6 ,  Sammer Yousuf  5 ,  M Iqbal Choudhary  7
Affiliations
  • 1. Department of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia.
  • 2. Department of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia; Department of Chemistry, Faculty of Science, Alexandria University, PO Box 426, Ibrahimia, 21321 Alexandria, Egypt. Electronic address: [email protected].
  • 3. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia; Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
  • 4. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
  • 5. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
  • 6. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
  • 7. Department of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia; H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
PMID: 26972921 DOI: 10.1016/j.bmc.2016.02.037
Abstract

A series of new malonamide derivatives were synthesized by Michael addition reaction of N(1),N(3)-di(pyridin-2-yl)malonamide into α,β-unsaturated ketones mediated by DBU in DCM at ambient temperature. The inhibitory potential of these compounds in vitro, against α-glucosidase enzyme was evaluated. Result showed that most of malonamide derivatives were identified as a potent inhibitors of α-glucosidase enzyme. Among all the compounds, 4K (IC50=11.7 ± 0.5 μM) was found out as the most active one compared to standard drug acarbose (IC50=840 ± 1.73 μM). Further cytotoxicity of 4a-4m were also evaluated against a number of Cancer and normal cell lines and interesting results were obtained.

Keywords
Cytotoxicity; Diabetes; Malonamide; Michael addition; Nitrogen heterocycles; α-Glucosidase.