Design, Molecular Docking, Synthesis and Evaluation of New Isatin Derivatives Bearing Pyridine Moiety as Potential Tyrosine Kinase Inhibitors

Document Type : Original Article


1 Department of Pharmaceutical Chemistry, College of Pharmacy, Mustansiriyah University, Baghdad- Iraq.

2 pharmaceutical chemistry department, college of pharmacy, Mustansiriyah University, Baghdad- Iraq.

3 Department of Pharmaceutical Chemistry, College of Pharmacy, Mustansiriyah University, Baghdad-Iraq.


A series of new 1-(3-imino-2-oxoindolin-5-yl)-3-phenylurea derivatives were synthesized starting from 5-aminoisatin; as a part of our program to compose multicomponent hybrid templates with potential pharmaceutical recognition and evaluate them as inhibitors of receptor tyrosine kinase. The proposed chemicals were synthesized and purified satisfactorily; They were classified and identified using a variety of methods: melting point, IR spectroscopy, 1H-NMR and13C-NMR; The effectiveness of these novel chemicals was tested for their in vitro cytotoxic activity and In silico tyrosine kinase selectivity through molecular docking via GOLD Suite (v.5.7.1); There is a good agreement between our docked results and the experimental results (In vitro study) since the compound 3a was the most potent cytotoxic scaffold shows the highest docking results and at the same time showing a promising antitumor activity among the tested compounds when tested against (A549) cancer cell lines by the MTT assay with IC50= 30.4 μM in comparison with erlotinib. Furthermore, using SWISS ADME, the drug likeness of these selected anti-proliferative drugs was anticipated based on their pharmacokinetics profiles. By not violating Lipinski's rule of five, the anti-proliferative drugs were determined to be orally safe. This study proposed a method for developing effective anti-proliferative drugs that target their target enzyme.


Main Subjects

  • Receive Date: 17 April 2021
  • Revise Date: 19 August 2021
  • Accept Date: 01 September 2021
  • First Publish Date: 01 September 2021