Physicochemical interaction of antitumor acridinone derivatives with DNA in view of QSAR studies

The acridinone derivatives with antitumor activity and ability with respect to noncovalent DNA binding were investigated for their quantitative structure–activity relationships (QSAR). Multiple regression analysis was used to model relationships between molecular descriptors and antileukemia activity, or between molecular descriptors and DNA-duplexes stabilization. Studies were performed on molecular modeling using HyperChem and Dragon computer programs, and molecular geometry optimization using MM+ molecular mechanics and semi-empirical AM1 method. Two multiple regression equations were derived and characterized as good and with statistically significant correlations, R = 0.9384 and R = 0.8388, for quantitative structure–antitumor activity relationships and quantitative structure–ability to DNA-duplexes stabilization relationships, respectively. Moreover, hydrophobic and total molecular symmetry properties are important for antitumor activity of acridinone derivatives, and electronic and topological properties are important for physicochemical (noncovalent) DNA-duplexes stabilization of these compounds. The obtained equations can be used for prediction of acridinone derivatives’ activity and their ability to noncovalent interaction with DNA which, as it was shown earlier, play important role in the antitumor mechanism of action of these compounds.