Multi-Component Reactions of Cyclohexan-1,3-dione: Synthesis of Fused Pyran, Pyridine, Thiophene and Pyrazole Derivatives with c-Met, Anti-Proliferative Activities

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

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

Volume 21 , Issue 17 , 2021


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Abstract:

Background: Recently, products of Multi-Component Reactions (MCR’s) acquired special attention due to their wide range of pharmacological activities especially therapeutic activities. Inthe market it was found that many pharmacological drugs containing the pyran and pyridine nucleus that were produced through MCR’s were found.

Objective: Thiswork aimsto synthesize target molecules not only possess anti-tumour activities but also c-Met and prostate cancer inhibitors. The target molecules were obtained starting from cyclohexan-1,3-dione through its multi-component reactions to produce anticancer target molecules.

Methods: Cyclohexane-1,3-dione underwent different multi-component reactions to produce fused pyran, pyridine and thiophene derivatives. The anti-proliferative activity of the newly synthesized compounds among the synthesized compounds toward the six cancer cell lines, namely A549, H460, HT-29, MKN-45, U87MG, and SMMC-7721 was studied. In addition, inhibitions toward c-Met kinase and prostate cancer cell line were studied. Antitumor evaluations toward seventeen cancer cell lines subpanel, for certain compounds, were also demonstrated according to the diseases. Pim-1 kinase inhibitions of the most active compounds were also measured.

Results: Anti-proliferative evaluations, c-Met and Pim-1 kinase inhibitions were performed for most of the synthesized compounds where the varieties of substituent through the aryl ring and the heterocyclic ring afforded compounds with high activities.

Conclusion: Compounds 4b, 6b, 8b, 9a, 11b, 12b, 17b, 18b, 19, 22c, 23b, 25b and 26b were the most cytotoxic compounds toward the six cancer cell lines. Inhibitions toward c-Met kinase and prostate cancer cells showed that the presence of the electronegative Cl group within the molecule wereresponsible for its high activity. In addition, inhibitions toward Pim-1 kinase exhibited that most of tested compounds showed high inhibitions.

Keywords: Cyclohexan-1, 3-dione, multi-component reactions, pyran, pyridine, thiophene, anti-proliferative.

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Article Details

VOLUME: 21
ISSUE: 17
Year: 2021
Published on: 11 January, 2021
Page: [2443 - 2463]
Pages: 21
DOI: 10.2174/1871520621666210112115128
Price: $95

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