Investigation of interactions of drugs used in cancer treatment with biomolecules by molecular modeling

An antracycline antibiotic doxorubicin and a glycopeptide antibiotic bleomycin with anti-tumor activity are produced by the bacterium Streptomyces peucetius and Streptomyces verticillus, respectively. The interactions between these drugs and genetic material and the details of the intercalation with DNA have been controversial issues. Thus, the interaction of doxorubicin and bithiazole tail of bleomycin with nucleobases were studied by quantum mechanical methods. For this purpose, conformational analyses of doxorubicin and bithiazole domain of bleomycin were performed with Spartan 08 software and 422 conformers for doxorubicin and 798 conformers for bleomycin were determined, respectively. In order to determine the most stable conformer, optimizations with Spartan 08 software were performed. Geometry optimizations and frequency analyses were performed for each conformer using density functional theory (DFT) at B3LYP/6-31G** level using Gaussian 09 software. Since the structure of bithiazole domain was different from initial 3D structure, further analyses were not performed. The most stable 20 conformers of doxorubicin and nucleobase tautomers were optimized again with ɷB97XD/6-31G** level and their interactions were also analysed at the same level. The Discovery Studio 3.5 Client programme was used to draw the initial and final structures of interaction geometries. The effect of solvent (water) on the structure of doxorubicin, nucleobase tatutomers and interactions of them were also studied and it was found that doxorubicin and nuclobases were interact each other at the tetracyclic reagion of doxorubicin and form hydrogen bonds.