Affiliations 

  • 1 Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia. Electronic address: taha_hej@yahoo.com
  • 2 Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia
  • 3 Department of Chemistry, Hazara University, Mansehra 21300, Khyber Pukhtunkhwa, 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
  • 6 Department of Chemistry, COMSATS Institute of Information Technology, University Road, Abbottabad 22060, KPK, Pakistan
Bioorg Chem, 2016 10;68:80-9.
PMID: 27474803 DOI: 10.1016/j.bioorg.2016.07.010

Abstract

Thymidine phosphorylase (TP) is up regulated in wide variety of solid tumors and therefore presents a remarkable target for drug discovery in cancer. A novel class of extremely potent TPase inhibitors based on benzopyrazine (1-28) has been developed and evaluated against thymidine phosphorylase enzyme. Out of these twenty-eight analogs eleven (11) compounds 1, 4, 14, 15, 16, 17, 18, 19, 20, 24 and 28 showed potent thymidine phosphorylase inhibitory potentials with IC50 values ranged between 3.20±0.30 and 37.60±1.15μM when compared with the standard 7-Deazaxanthine (IC50=38.68±4.42μM). Structure-activity relationship was established and molecular docking studies were performed to determine the binding interactions of these newly synthesized compounds. Current studies have revealed that these compounds established stronger hydrogen bonding networks with active site residues as compare to the standard compound 7DX.

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