Synthesis, molecular docking study and in vitro thymidine phosphorylase inhibitory potential of oxadiazole derivatives

Ullah H 1 , Rahim F 2 , Taha M 3 , Uddin I 1 , Wadood A 4 , Shah SAA 5 Show all authors , Farooq RK 6 , Nawaz M 1 , Wahab Z 7 , Khan KM 8

Affiliations 

  • 1 Department of Chemistry, Hazara University, Mansehra 21300, Pakistan
  • 2 Department of Chemistry, Hazara University, Mansehra 21300, Pakistan. Electronic address: fazalstar@gmail.com
  • 3 Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia. Electronic address: mtaha@iau.edu.sa
  • 4 Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan
  • 5 Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D.E., Malaysia
  • 6 Department of Neuroscience Research, Institute of Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
  • 7 Department of Conservation Sciences, Hazara University, Mansehra 21300, Pakistan
  • 8 Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia; H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
Bioorg Chem, 2018 08;78:58-67.
PMID: 29533215 DOI: 10.1016/j.bioorg.2018.02.020

Abstract

We have synthesized oxadiazole derivatives (1-16), characterized by 1H NMR, 13C NMR and HREI-MS and screened for thymidine phosphorylase inhibitory potential. All derivatives display varied degree of thymidine phosphorylase inhibition in the range of 1.10 ± 0.05 to 49.60 ± 1.30 μM when compared with the standard inhibitor 7-Deazaxanthine having an IC50 value 38.68 ± 1.12 μM. Structure activity relationships (SAR) has been established for all compounds to explore the role of substitution and nature of functional group attached to the phenyl ring which applies imperious effect on thymidine phosphorylase activity. Molecular docking study was performed to understand the binding interaction of the most active derivatives with enzyme active site.

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