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 1982, Dammam 31441, 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 D. E, Malaysia; Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar, Puncak Alam, Selangor Darul Ehsan, Malaysia
  • 6 College of Computer Science & Information Technology (CCSIT), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 3144, Saudi Arabia
  • 7 Department of Pharmacy, University of Malakand, Chakdara, Dir (L), Khyber-Pakhtunkhwa (KPK) 18000, Pakistan
  • 8 Department of Pharmacy, Sarhad University of Science & Information Technology, Peshawar, Pakistan
Bioorg. Chem., 2019 08;89:102999.
PMID: 31151055 DOI: 10.1016/j.bioorg.2019.102999

Abstract

Isoquinoline analogues (KA-1 to 16) have been synthesized and evaluated for their E. coli thymidine phosphorylase inhibitory activity. Except compound 11, all other analogs showed outstanding thymidine inhibitory potential ranging in between 4.40 ± 0.20 to 69.30 ± 1.80 µM when compared with standard drug 7-Deazaxanthine (IC50 = 38.68 ± 4.42 µM). Structure Activity Relationships has been established for all compounds, mainly based on substitution pattern on phenyl ring. All analogs were characterized by various spectroscopic techniques such as 1H NMR, 13C NMR and EI-MS. The binding interactions of isoquinoline analogues with the active site of TP enzyme, the molecular docking studies were performed. Furthermore, the angiogenic inhibitory potentials of isoquinoline analogues (KA-1-9, 14, 12 and 16) were determined in the presence of standard drug Dexamethasone based on percentage inhibitions at various concentrations. Herein this work analogue KA-12, 14 and 16 emerged with most potent angiogenic inhibitory potentials among the synthesized analogues.

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