Synthesis and Cytotoxic Evaluation of 3-Methylidenechroman-4-ones
AbstractIn the search for new anticancer agents, a library of variously substituted 3-methylidenechroman-4-ones was synthesized using Horner–Wadsworth–Emmons methodology. Acylation of diethyl methylphosphonate with selected ethyl salicylates furnished 3-diethoxyphosphorylchromen-4-ones which were next used as Michael acceptors in the reaction with various Grignard reagents. The adducts were obtained as the mixtures of trans and cis diastereoisomers along with a small amount of enol forms. Their relative configuration and preferred conformation were established by NMR analysis. The adducts turned up to be effective Horner–Wadsworth–Emmons reagents giving 2-substituted 3-methylidenechroman-4-ones, which were then tested for their possible cytotoxic activity against two leukemia cell lines, HL-60 and NALM-6, and against MCF-7 breast cancer cell line. All new compounds (14a–o) were highly cytotoxic for the leukemic cells and showed a moderate or weak effect on MCF-7 cells. Analog 14d exhibited the highest growth inhibitory activity and was more potent than carboplatin against HL-60 (IC50 = 1.46 ± 0.16 µM) and NALM-6 (IC50 = 0.50 ± 0.05 µM) cells. Further tests showed that 14d induced apoptosis in NALM-6 cells, which was mediated mostly through the extrinsic pathway. View Full-Text
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Kędzia, J.; Bartosik, T.; Drogosz, J.; Janecka, A.; Krajewska, U.; Janecki, T. Synthesis and Cytotoxic Evaluation of 3-Methylidenechroman-4-ones. Molecules 2019, 24, 1868.
Kędzia J, Bartosik T, Drogosz J, Janecka A, Krajewska U, Janecki T. Synthesis and Cytotoxic Evaluation of 3-Methylidenechroman-4-ones. Molecules. 2019; 24(10):1868.Chicago/Turabian Style
Kędzia, Jacek; Bartosik, Tomasz; Drogosz, Joanna; Janecka, Anna; Krajewska, Urszula; Janecki, Tomasz. 2019. "Synthesis and Cytotoxic Evaluation of 3-Methylidenechroman-4-ones." Molecules 24, no. 10: 1868.
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