Activation of trans geometry in bifunctional mononuclear platinum complexes by a non-bulky methylamine ligand
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
23770803
DOI
10.1016/j.jinorgbio.2013.05.009
PII: S0162-0134(13)00122-0
Knihovny.cz E-zdroje
- Klíčová slova
- Activation of trans geometry, Cytotoxicity, DNA adducts, Platinum(II)-based agents,
- MeSH
- adukty DNA chemie MeSH
- bezbuněčný systém MeSH
- cisplatina chemie farmakologie MeSH
- genetická transkripce MeSH
- lidé MeSH
- ligandy MeSH
- methylaminy chemie MeSH
- molekulární konformace MeSH
- molekulární sekvence - údaje MeSH
- nádorové buněčné linie MeSH
- organoplatinové sloučeniny chemická syntéza farmakologie MeSH
- platina chemie MeSH
- protinádorové látky chemická syntéza farmakologie MeSH
- sekvence nukleotidů MeSH
- vazebná místa MeSH
- viabilita buněk účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adukty DNA MeSH
- cisplatina MeSH
- ligandy MeSH
- methylamine MeSH Prohlížeč
- methylaminy MeSH
- organoplatinové sloučeniny MeSH
- platina MeSH
- protinádorové látky MeSH
- transplatin MeSH Prohlížeč
In order to shed light on the mechanism that underlies activity of bifunctional mononuclear Pt(II) analogs of transplatin we examined in the present work a DNA binding mode of the analog of transplatin, namely trans-[Pt(CH3NH2)2Cl2], in which NH3 groups were replaced only by a small, non-bulky methylamine ligand. This choice was made because we were interested to reveal the role of the bulkiness of the amines used to substitute NH3 in transplatin to produce antitumor-active Pt(II) drug. The results indicate that trans-[Pt(CH3NH2)2Cl2] forms a markedly higher amount of more distorting intrastrand cross-links than transplatin which forms in DNA preferentially less distorting and persisting monofunctional adducts. Also importantly, the accumulation of trans-[Pt(CH3NH2)2Cl2] in tumor cells was considerably greater than that of transplatin and cisplatin. In addition, the results of the present work demonstrate that the replacement of ammine groups by the non-bulky methylamine ligand in the molecule of ineffective transplatin results in a radical enhancement of its activity in tumor cell lines including cisplatin-resistant tumor cells. Thus, activation of the trans geometry in bifunctional mononuclear Pt(II) complexes can be also accomplished by replacement of ammine groups in transplatin by non-bulky methylamine ligands so that it is not limited only to the replacement by relatively bulky and stereochemically more demanding amino ligands.
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