Dihydropyrimidones: As novel class of β-glucuronidase inhibitors

Ali F 1 , Khan KM 2 , Salar U 1 , Iqbal S 1 , Taha M 3 , Ismail NH 4 Show all authors , Perveen S 5 , Wadood A 6 , Ghufran M 6 , Ali B 1

Affiliations 

  • 1 H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
  • 2 H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: khalid.khan@iccs.edu
  • 3 Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D.E., Malaysia; Faculty of Applied Science, Universiti Teknologi MARA, Shah Alam 40450, Selangor D.E., Malaysia
  • 4 Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D.E., Malaysia
  • 5 PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan
  • 6 Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University Mardan, Pakistan
Bioorg Med Chem, 2016 08 15;24(16):3624-35.
PMID: 27325448 DOI: 10.1016/j.bmc.2016.06.002

Abstract

Dihydropyrimidones 1-37 were synthesized via a 'one-pot' three component reaction according to well-known Biginelli reaction by utilizing Cu(NO3)2·3H2O as catalyst, and screened for their in vitro β-glucuronidase inhibitory activity. It is worth mentioning that amongst the active molecules, compounds 8 (IC50=28.16±.056μM), 9 (IC50=18.16±0.41μM), 10 (IC50=22.14±0.43μM), 13 (IC50=34.16±0.65μM), 14 (IC50=17.60±0.35μM), 15 (IC50=15.19±0.30μM), 16 (IC50=27.16±0.48μM), 17 (IC50=48.16±1.06μM), 22 (IC50=40.16±0.85μM), 23 (IC50=44.16±0.86μM), 24 (IC50=47.16±0.92μM), 25 (IC50=18.19±0.34μM), 26 (IC50=33.14±0.68μM), 27 (IC50=44.16±0.94μM), 28 (IC50=24.16±0.50μM), 29 (IC50=34.24±0.47μM), 31 (IC50=14.11±0.21μM) and 32 (IC50=9.38±0.15μM) found to be more potent than the standard d-saccharic acid 1,4-lactone (IC50=48.4±1.25μM). Molecular docking study was conducted to establish the structure-activity relationship (SAR) which demonstrated that a number of structural features of dihydropyrimidone derivatives were involved to exhibit the inhibitory potential. All compounds were characterized by spectroscopic techniques such as (1)H, (13)C NMR, EIMS and HREI-MS.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

MeSH terms
Similar publications