Three potential anticancer agents {trans-[PtCl(2)(NH(3))(thiazole)], cis-[PtCl(2)(NH(3))(piperidine)], and PtCl(2)(NH(3))(cyclohexylamine) (JM118)} were explored and compared with cisplatin and the inactive [PtCl(dien)](+) complex. Basic electronic properties, bonding and stabilization energies were determined, and thermodynamic and kinetic parameters for the aquation reaction were estimated at the B3LYP/6-311++G(2df,2pd) level of theory. Since the aquation process represents activation of these agents, the obtained rate constants were compared with the experimental IC(50) values for several tumor cells. Despite the fact that the processes in which these drugs are involved and the way in which they affect cells are very complex, some correlations can be deduced.

• MeSH
• chemické modely * MeSH
• cisplatina chemie   farmakologie   MeSH
• elektrony MeSH
• inhibiční koncentrace 50 MeSH
• kinetika MeSH
• lidé MeSH
• ligandy MeSH
• nádorové buněčné linie MeSH
• organoplatinové sloučeniny chemie   farmakologie   MeSH
• počítačová simulace * MeSH
• protinádorové látky chemie   farmakologie   MeSH
• sloučeniny platiny chemie   MeSH
• termodynamika MeSH
• thiazoly chemie   farmakologie   MeSH
• voda chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• amminedichloro(cyclohexylamine)platinum(II) MeSH Prohlížeč
• cisplatina MeSH
• ligandy MeSH
• organoplatinové sloučeniny MeSH
• platinum chloride MeSH Prohlížeč
• protinádorové látky MeSH
• sloučeniny platiny MeSH
• thiazoly MeSH
• trans-(PtCl2(NH3)(thiazole)) MeSH Prohlížeč
• voda MeSH

In this study, various platinum cross-links in DNA bases were explored. Some of these structures occur in many cis/trans-platinated double-helixes or single-stranded adducts. However, in the models studied, no steric hindrance from sugar-phosphate backbone or other surroundings is considered. Such restrictions can change the bonding picture partially but hopefully the basic energy characteristics will not be changed substantially. The optimization of the structures explored was performed at the DFT level with the B3LYP functional and the 6-31G(d) basis set. Perturbation theory at the MP2/6-31++G(2df,2pd) level was used for the single-point energy and 6-31+G(d) basis set for the electron-property analyses. It was found that the most stable structures are the diguanine complexes followed by guanine-cytosine Pt-cross-links, ca 5 kcal mol(-1) less stable. The adenine-containing complexes are about 15 kcal mol(-1) below the stability of diguanine structures. This stability order was also confirmed by the BE of Pt-N bonds. For a detailed view on dative and electrostatic contributions to Pt-N bonds, Natural Population Analysis, determination of electrostatic potentials, and canonical Molecular Orbitals description of the examined systems were used.

• MeSH
• adenin chemie   MeSH
• cisplatina chemie   MeSH
• cytosin chemie   MeSH
• guanin chemie   MeSH
• heteroduplexy nukleové kyseliny chemie   MeSH
• jednovláknová DNA chemie   MeSH
• molekulární modely MeSH
• platina chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenin MeSH
• cisplatina MeSH
• cytosin MeSH
• guanin MeSH
• heteroduplexy nukleové kyseliny MeSH
• jednovláknová DNA MeSH
• platina MeSH