In vitro and in vivo biological activity screening of Ru(III) complexes involving 6-benzylaminopurine derivatives with higher pro-apoptotic activity than NAMI-A
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
21536006
DOI
10.1016/j.jinorgbio.2011.04.002
PII: S0162-0134(11)00082-1
Knihovny.cz E-zdroje
- MeSH
- apoptóza účinky léků MeSH
- benzylové sloučeniny MeSH
- dimethylsulfoxid analogy a deriváty farmakologie MeSH
- kinetin chemická syntéza chemie farmakologie MeSH
- komplexní sloučeniny chemická syntéza chemie farmakologie MeSH
- krystalografie rentgenová MeSH
- leukemie L1210 farmakoterapie patologie MeSH
- lidé MeSH
- mitóza účinky léků MeSH
- molekulární konformace MeSH
- myši inbrední DBA MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nekróza MeSH
- organokovové sloučeniny farmakologie MeSH
- protinádorové látky chemická syntéza chemie farmakologie MeSH
- puriny MeSH
- ruthenium * MeSH
- screeningové testy protinádorových léčiv MeSH
- sloučeniny ruthenia MeSH
- transplantace nádorů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- benzylaminopurine MeSH Prohlížeč
- benzylové sloučeniny MeSH
- dimethylsulfoxid MeSH
- imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III) MeSH Prohlížeč
- kinetin MeSH
- komplexní sloučeniny MeSH
- organokovové sloučeniny MeSH
- protinádorové látky MeSH
- puriny MeSH
- ruthenium * MeSH
- sloučeniny ruthenia MeSH
A series of novel octahedral ruthenium(III) complexes involving 6-benzylaminopurine (L) derivatives as N-donor ligands has been prepared by the reaction of [(DMSO)(2)H][trans-RuCl(4)(DMSO)(2)] with the corresponding L derivative. The complexes 1-12 have the general compositions trans-[RuCl(4)(DMSO)(n-Cl-LH)]⋅xSol (1-3), trans-[RuCl(4)(DMSO)(n-Br-LH)]·xSol (4-6), trans-[RuCl(4)(DMSO)(n-OMe-LH)]·xSol (7-9) and trans-[RuCl(4)(DMSO)(n-OH-LH)]·xSol (10-12); n=2, 3, and 4, x=0-1.5; and Sol = H(2)O, DMSO, EtOH and/or (Me)(2)CO. The complexes have been thoroughly characterized by elemental analysis, UV-visible, FTIR, Raman, and EPR spectroscopy, ES+(positive ionization electrospray) mass spectrometry, thermal analysis, cyclic voltammetry, magnetic and conductivity measurements. The X-ray molecular structure of trans-[RuCl(4)(DMSO)(3-Br-LH)]⋅(Me)(2)CO (5) revealed the distorted octahedral coordination in the vicinity of the central atom, and also confirmed that the 3-Br-L ligand is present as the N3-protonated N7-H tautomer and is coordinated to Ru(III) through the N9 atom of the purine moiety. The tested complexes have been found to be in vitro non-cytotoxic against K562, G361, HOS and MCF7 human cancer cell lines with IC(50)>100μM in contrast to the moderate results regarding the antiradical activity with IC(50)≈10(-3)M. On the contrary, in vivo antitumor activity screening showed that the prepared Ru(III) complexes possess higher pro-apoptotic activity than NAMI-A. The reduction of Ru(III) to Ru(II) and Ru(II)-species formation in tumor tissues was confirmed by means of a simple method of detection and visualization of intracellular Ru(II) by fluorescence microscopy. The originality of this method is based on the preparation of a Ru(II)-bipyridine complex in situ.
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