Synthesis, β-glucuronidase inhibition and molecular docking studies of hybrid bisindole-thiosemicarbazides analogs

Taha M 1 , Ismail NH 2 , Imran S 2 , Rahim F 3 , Wadood A 4 , Khan H 4 Show all authors , Ullah H 3 , Salar U 5 , Khan KM 5

Affiliations 

  • 1 Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Puncak Alam 42300, Malaysia; Faculty of Applied Science, Universiti Teknologi MARA, Shah Alam 40450, Selangor D.E., Malaysia. Electronic address: [email protected]
  • 2 Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Puncak Alam 42300, Malaysia; Faculty of Applied Science, Universiti Teknologi MARA, Shah Alam 40450, Selangor D.E., Malaysia
  • 3 Department of Chemistry, Hazara University, Mansehra-21300, Khyber Pakhtunkhwa, Pakistan
  • 4 Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University Mardan, Pakistan
  • 5 H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
Bioorg Chem, 2016 10;68:56-63.
PMID: 27454618 DOI: 10.1016/j.bioorg.2016.07.008

Abstract

Hybrid bisindole-thiosemicarbazides analogs (1-18) were synthesized and screened for β-glucuronidase activity. All compounds showed varied degree of β-glucuronidase inhibitory potential when compared with standard d-saccharic acid 1,4-lactone (IC50=48.4±1.25μM). Compounds 4, 7, 9, 6, 5, 12, 17 and 18 showed exceptional β-glucuronidase inhibition with IC50 values ranging from 0.1 to 5.7μM. Compounds 1, 3, 8, 16, 13, 2 and 14 also showed better activities than standard with IC50 values ranging from 7.12 to 15.0μM. The remaining compounds 10, 11, and 15 showed good inhibitory potential with IC50 values 33.2±0.75, 21.4±0.30 and 28.12±0.25μM respectively. Molecular docking studies were carried out to confirm the binding interaction of the compounds.

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

MeSH terms
Similar publications