The effect of all phenol groups on the growth of cancer cells was examined. Among these compounds derived by acylation, alkylation and substitution, 4a, 4b, 6a, 7b, 9 and 11 exhibited acceptable anti-proliferative activity within the range of 10–20 lM IC50, whereas the other derivatives displayed very minimal inhibitory activity. This SAR data suggests that the phenol functional groups, especially at C3 and C6 position should play an important role in addressing the cytotoxicity of the xanthones.