Title:The Uses of Dimedone for the Synthesis of Thiophene, Thiazole and Annulated Derivatives with Antitumor, Pim-1 Kinase Inhibitions, PAINS Evaluations and Molecular Docking
Volume: 21
Issue: 16
Author(s): Wagnat W. Wardakhan*, Amira M. Elmetwally, Abeer A. Mohamed and Rafat M. Mohareb
Affiliation:
- National Organization for Drug Control and Research (NODCAR) P.O. 29, Cairo,Egypt
Keywords:
Dimedone, arylhydrazone, thiophene, pyran, anti-proliferative activity, molecular docking.
Abstract:
Background: Dimedone is considered as one of the most important classes of compounds belonging
to cyclohexan-1,3-dione. Such groups of compounds were considered as precursors for many pharmaceutically
active heterocyclic compounds.
Objective: The target molecules in this work were synthesized from arylhydrazones of dimedone with different
substituents enhancing the study of their structure-activity relationship.
Methods: Arylhydrazones of dimedones were subjected to a series of heterocyclization reactions affording annulated
compounds. The anti-proliferative activities of the synthesized molecules were evaluated against six
cancer cell lines. In addition, inhibitions toward tyrosine kinases, Pim-1 kinases and PAINS of the most active
compounds were also studied. c-Met enzymatic inhibitions and molecular docking studies were carried out for
three compounds.
Results: Anti-cancer evaluations together with tyrosine and Pim-1 kinases of most of the synthesized compounds
were carried out through this work. The study revealed that changing of substituents had a strong impact
on the activity of the molecule.
Conclusion: Many of the synthesized compounds exhibited high inhibitions towards the six cancer cell lines.
This will encourage further work through the synthesis of target molecules with the same ring systems. The
three compounds 7b, 8c and 12b that revealed excellent inhibitions were tested against c-Met kinase and their
molecular modelling was expressed.
