Quantitative activity relationship (QSAR) has been carried out in a series of 1,5-di(4-amidino phenoxy)pentane & its analogues against Topoisomerase II inhibitory activities. The 2D QSAR studies activity is negatively influenced by the presence of linker (O or N), contribution of hydrophobicity and substitution on para position contributed in molar refractivity. The best QSAR model with good correlation coefficient (r2 =0.712), of high statistical significance (> 99.9%) well explained the variance in activity.