Herein we report the synthesis of a series of O-alkyl oximes of flavone and 6-hydroxyflavone using a simple experimental protocol under solvent free conditions with yields up to 87%.Cytotoxicity of all compounds was evaluated against MDA-MB-231, PC-3, A-549 and MRC-5 cells.IC 50 values for two compounds were determined to be in the range 28.7-47.8μM against all tested cell lines.Oxime ethers derivatives showed IC 50 values between 28.7 and 49.5 μM against MDA-MB-231, while the best activity was obtained for 6-hydroxyflavone with an IC 50 of 3.4 μM against this cell line.Compounds containing the substituent hydroxyl at the position six of flavone system displayed the best antiproliferative activity over MDA-MB-231 cells, being necessary this group to improve the sensibility on this type of cells.The antiproliferative activity of 6-hydroxyflavone is drastically diminished when the carbonyl group of flavone is changed by an oxime ether.