The Uses of Dimedone for the Synthesis of Thiophene, Thiazole and Annulated Derivatives with Antitumor, Pim-1 Kinase Inhibitions, PAINS Evaluations and Molecular Docking

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Author(s): Wagnat W. Wardakhan*, Amira M. Elmetwally, Abeer A. Mohamed, Rafat M. Mohareb

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

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Abstract:

Background: Dimedone is considered as one of the most important class of compounds belonging to cyclohexan-1,3-dione. Such group of compounds were considered as precursors for many pharmaceutically active heterocyclic compounds.

Objective: The target molecules through this work were synthesized from arylhydrazones of dimedone with different substituent’s enhancing study of their structure activity relationship.

Methods: Arylhydrazones of dimedones were subjected to a series of heterocyclization reactions affording annulated compounds. The antiproliferative 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 studied were carried 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 substituent had a strong impact on the activity of themolecule.

Conclusion: Many of the synthesized compounds exhibited high inhibitions toward the six cancer cell lines and this will encourage further work through the synthesis of target molecule 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.

Keywords: Dimedone, arylhydrazone, thiophene, pyran, anti-proliferative activity, molecular docking

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1871520621666210119092325
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