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Design, synthesis and biological evaluation of novel 5-hydroxy-2-methyl-4H-pyran-4-one derivatives as antiglioma agents.

ABSTRACT: d-2-Hydroxyglutarate (d-2HG) is frequently found in human brain cancers. Approximately 50-80% of grade II glioma patients have a high level of d-2HG production, which can lead to cancer initiation. In this study, a series of novel 5-hydroxy-2-methyl-4H-pyran-4-one derivatives were designed and synthesized as antiglioma agents, and their related structure-activity relationships are discussed. Among these novel compounds, 4a exhibited promising anti-proliferative activity against glioma HT1080 cells and U87 cells with an IC₅₀ of 1.43 ?M and 4.6 ?M, respectively. Further studies found that the most active compound (4a) shows an 86.3% inhibitory rate against the intracellular production of d-2HG at 1 ?M, and dramatic inhibitory effects, even at 1 ?M on the colony formation and migration of U87 and HT1080 cells.

SUBMITTER: Li YB

PROVIDER: S-EPMC6071749 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Design, synthesis and biological evaluation of novel 5-hydroxy-2-methyl-4H-pyran-4-one derivatives as antiglioma agents.

Li Yi-Bin YB Hou Wen W Lin Hui H Sun Ping-Hua PH Lin Jing J Chen Wei-Min WM

MedChemComm 20180119 3

d-2-Hydroxyglutarate (d-2HG) is frequently found in human brain cancers. Approximately 50-80% of grade II glioma patients have a high level of d-2HG production, which can lead to cancer initiation. In this study, a series of novel 5-hydroxy-2-methyl-4H-pyran-4-one derivatives were designed and synthesized as antiglioma agents, and their related structure-activity relationships are discussed. Among these novel compounds, 4a exhibited promising anti-proliferative activity against gli ...[more]

PMID: 30108937

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