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Cisplatin and oxaliplatin are two widely-used anti-cancer drugs which covalently bind to a same location in DNA strands. Platinum agents make intrastrand and interstrand cross-links with the N7 atoms of guanine nucleotides which prevent DNA from polymerization by causing a distortion in the double helix. Molecular dynamics simulations and free energy calculations were carried out to investigate the binding of two platinum-based anti-cancer drugs with DNA. We compared the binding of these drugs which differ in their carrier ligands, and hence their potential interactions with DNA. When a platinum agent binds to nucleotides, it causes a high amount of deformation in DNA structure. To find the extent of deformation, torsion angles and base pair and groove parameters of DNA were considered. These parameters were compared with normal B-DNA which was considered as the undamaged DNA. The formation of hydrogen bonds between drugs and DNA nucleotides was examined in solution. It was shown that oxaliplatin forms more hydrogen bonds than cisplatin. Our results confirm that the structure of the platinated DNA rearranges significantly and cisplatin tries to deform DNA more than oxaliplatin. The binding free energies were also investigated to understand the affinities, types and the contributions of interactions between drugs and DNA. It was concluded that oxaliplatin tendency for binding to DNA is more than cisplatin in solvent environment. The binding free energy was calculated based on the MM/PBSA and MM/GBSA methods and the results of QM/MM calculations verified them.

Both sulforaphane (SF) and cisplatin (CP) are well-known anticancer drugs and in some cases, they are used simultaneously for the treatment of a wide range of cancers. SF is the main component of cruciferous vegetables such as broccoli. CP is a four-coordinated complex of platinum, Pt(NH₃)Cl₂. The interaction of SF with CP is important since a ligand of this inorganic complex might be replaced by SF. In this work, the complexation of SF with CP has been studied theoretically using an accurate high-level ab initio method, together with a reliable method of density functional theory method. Calculations are extended to solution phase by means of solvation model density. Different functional groups of SF are investigated so that the most active site of SF in reaction with CP is determined from both thermodynamics and kinetics points of view. Derivatives of SF have been also studied in order to improve their solbilities in aqueous solution. The results of this work show that SF can form a stable complex with CP and interactions of these two compounds should be considered.