Computational Procedure for Determining Physicochemical Properties of Doxorubicin-TPGS and Daunorubicin-TPGS as Anticancer Agents

摘要

Daunorubicin (or daunomycin) and Doxorubicin (or adriamycin or 14-hydroxydaunomycin) are well-known anti-cancer agents used in cancer chemotherapy. They are anthracycline antibiotics and are commonly used in the treatment of a wide range of cancers. Doxorubicin and Daunorubicin were chemically conjμgated to TPGS(Doxorubicin conjμgated to D-a -tocopheryl polyethylene glycol 1000 succinate which unit number of polyethylene glycol in the study is four and Doxorubicin-TPGS is complex A and Daunorubicin-TPGS is complex B) Complex A and B are large molecules. 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 of this approach for optimization of complex A and B. In this research, the molecular structure, Binding Energy (BE), Dipole Moment (DM), Gibbs free energy of solvation (ΔG _((SOlVatlon))) and some physicochemical properties of the Doxorubicin- TPGS and Daunorubicin-TPGS were investigated. Our results indicate that these complexes mentioned above can be used to improve the anti-cancer activity and the water-solubility of Doxorubicin and Daunorubicin.