Doxorubicin is a drug used in cancer chemotherapy. It is an anthracycline antibiotic and it is commonly used in the treatment of a wide range of cancers. In this report, the molecular structure, Binding Energy(BE), Dipole Moment (DM), Gibbs free energy of solvation (
G (solvation)) and some physicochemical properties of DOX-GA3(glucuronide prodrug of doxorubicin) and DOX-mGA3(methylester of the glucuronide prodrug) conjugated complexs were investigated using computational methods . For large reactive systems, the calculation of energies can be simplified by treating the active part with a high-level quantum mechanical (QM) ab initio or density functional. One such method is the original ‘‘Our-own-N-layer Integrated molecular Orbital, Molecular Mechanics ONIOM’’ approach. We used this approach for optimization of DOX-GA3 and DOX-mGA3 complexs.Our results indicate that these complexs mentioned above can be used to improve anti cancer activity and water-solubility of Doxorubicin.