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

Hayat Ullah; Fazal Rahim; Muhammad Taha; Imad Uddin; Abdul Wadood; Syed Adnan Ali Shah; Rai Khalid Farooq; Mohsan Nawaz; Zainul Wahab; Khalid Mohammed Khan

doi:10.1016/j.bioorg.2018.02.020

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

Bioorg Chem. 2018 Aug:78:58-67. doi: 10.1016/j.bioorg.2018.02.020. Epub 2018 Mar 7.

Authors

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.

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.

Keywords: Molecular docking; Oxadiazole; SAR; Synthesis; Thymidine phosphorylase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Dose-Response Relationship, Drug
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Molecular Docking Simulation*
Molecular Structure
Oxadiazoles / chemical synthesis
Oxadiazoles / chemistry
Oxadiazoles / pharmacology*
Structure-Activity Relationship
Thymidine Phosphorylase / antagonists & inhibitors*
Thymidine Phosphorylase / metabolism

Substances

Enzyme Inhibitors
Oxadiazoles
Thymidine Phosphorylase