American Chemical Society
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Novel Synthesis, Cytotoxic Evaluation, and Structure−Activity Relationship Studies of a Series of α-Alkylidene-γ-lactones and Lactams

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journal contribution
posted on 2005-05-19, 00:00 authored by Tomasz Janecki, Edyta Błaszczyk, Kazimierz Studzian, Anna Janecka, Urszula Krajewska, Marek Różalski
5-Alkyl- and 5-arylalkyl-3-methylenedihydrofuran-2-ones 13ae, 3-alkylidenedihydrofuran-2-ones 18ac, and 3-methylenepyrrolidin-2-ones 16ae were synthesized utilizing ethyl 2-diethoxyphosphoryl-4-nitroalkanoates 9ae as common intermediates. All obtained compounds were tested against L-1210, HL-60, and NALM-6 leukemia cells. The highest cytotoxic activity was observed for 3-methylenefuranones 13d,e bearing benzyl or 3,4-dimethoxyphenylmethyl substituents at position 5, with IC50 values of 5.4 and 6.0 μM, respectively. Contrary to the literature reports, no enhancement in activity due to the presence of a hydroxy group was found when the cytotoxicity of furanones 13a,b,d and 5-(1‘-hydroxyalkyl)-3-methylenedihydrofuran-2-ones 6a,b,d was compared. The anticancer activity of pyrrolidinones 16ae and 3-alkylidenefuranones 18ac was much weaker than that of furanones 13ae.