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• W2150475298 abstract "Two 4-methylideneisoxazolidin-5-ones (4a,b), which are alpha-methylidene-gamma-lactones containing a nitrogen atom in the lactone ring, were synthesized. Their cytotoxic properties were evaluated against promyelocytic leukemia HL-60 cells. Both 4a and 4b exhibited relatively high cytotoxic activity with an IC(50) of 4.1 and 5.4 microM, respectively. Caspase-3 activity assay revealed that both isoxazolidinones (4) were able to induce apoptosis process in time- and concentration-dependent manner. Using multiplex PCR analysis, it was observed that 4 caused distinct inhibition of BCL-2 gene expression. Expression of BAX, a pro-apoptotic gene remained unchanged. It was also found that 4a,b did not induce the expression of MDR1 and MRP1 genes, related to multidrug resistance. In addition, cytotoxicity data obtained for drug-sensitive and drug-resistant HL-60 ADR cells revealed that the investigated compounds were poor substrates for transport by MRP1 efflux pump, suggesting that they might be useful for treating drug-resistant tumors. Furthermore, antimicrobial properties of 4a,b were evaluated. They showed significant activity against fungi Candida albicans, but only a weak activity against all tested Gram-positive and Gram-negative bacterial strains." @default.
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• W2150475298 date "2007-02-01" @default.
• W2150475298 modified "2023-10-13" @default.
• W2150475298 title "Synthesis and biological evaluation of 4-methylideneisoxazolidin-5-ones – A new class of highly cytotoxic α-methylidene-γ-lactones" @default.
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• W2150475298 doi "https://doi.org/10.1016/j.ejmech.2006.09.005" @default.
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