A series of substituted chalcones was synthesised and screened for cytotoxic activity against the K562 human leukaemia cell line.(E)-3-(3 ″-Hydroxy-4 ″-methoxyphenyl)-2-methyl-1- (3′, 4′, 5′-trimethoxyphenyl)-prop-2-en-1-one [IC50 (K562) 0.21 nM] was found to be the most active. A relationship between the conformation and cytotoxicity of the chalcones is discussed.