Theoretical Study Of Anticancer Property For Cisplatinum Drugs

In this paper, we have mainly focused on the interaction between cisplatin and DNA. The potential relationship of cisplatin structure with its anticancer activity property has been investigated using quantum chemical method. In addition, we've also considered the influence of circumstance on the reaction. Comprehensive ab initio calculations were performed on the coordination of Pt(II), Pd(II) and Ni(II) adducts to the N(7) of guanine and guanine-cytosine (GC) base pair. The fully optimized geometries of the metal complexes were obtained and the stabilization energies of the interaction between metal adducts and nucleobase were calculated with B3LYP method by using 6-31* basis set for the light atom. While the effective core potential (ECP) is used for metal cation. The results show that both cispalladium and cisnickel cause similar geometric changes of the base pair as cisplatin. For the coordination of metal adducts to guanine, platinum adduct possesses the highest stabilization energy; but the interaction between metal-guanine and cytosine for nickel is larger than that for platinum and palladium. It is worthy to note that hydrolysis effect can also cause significant changes in H-bonds. The influence of binding of cisplatin adducts on tautomeric equilibria of DNA base guanine was investigated using quantum chemical method. The monoaqua adducts [Pt(NH3)2Cl(H2O)]+ and the diaqua species [Pt(NH3)2(H2O)2]2+ were chosen for coordination to the N7 site of guanine tautomers. The results demonstrate that the platinum adducts influence moderately on tautomeric equilibria but do not change the relative stability of tautomers whether in gas phase or in aqueous solution. The (1, 9) form having H atom at N1 and N9 is always the predominant structure when cisplatin adducts bound to guanine. However, other forms could coexist in water. Meanwhile, the calculations suggest the tautomeric equilibria may be via the same intermediate. Oxaliplatin is a new anticancer drug in recent years. We have compared the reactivity of oxaliplatin and cisplatin, toward adenine, guanine and methionine at B3LYP 6-31+G*/LanL2DZ level. Our calculations show two platinum drugs have moderate differences at structure and reactivity. This could result from steric effect of cyclohexane. The depurination reaction of guansine, protonated or modified with cisplatin at the N7 position, has been studied by density functional theory (DFT), computional results suggest both Protonation and platination accelerate the depurination reaction in gas phase. The study can not explain the anticancer mechanism of platinum drugs, but provide a guideline toward further understanding its special activity.