The first iron(III) complexes with cyclin-dependent kinase inhibitors: Magnetic, spectroscopic (IR, ES+ MS, NMR, (57)Fe Mössbauer), theoretical, and biological activity studies
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
20056279
DOI
10.1016/j.jinorgbio.2009.12.002
PII: S0162-0134(09)00307-9
Knihovny.cz E-zdroje
- MeSH
- elektrochemické techniky metody MeSH
- inhibiční proteiny cyklin-dependentních kinas * chemie metabolismus MeSH
- lidé MeSH
- molekulární modely MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- protinádorové látky chemická syntéza chemie farmakologie MeSH
- puriny chemie MeSH
- screeningové testy protinádorových léčiv MeSH
- spektrální analýza metody MeSH
- železo chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- inhibiční proteiny cyklin-dependentních kinas * MeSH
- protinádorové látky MeSH
- puriny MeSH
- železo MeSH
The first Fe(III) complexes 1-6 with cyclin-dependent kinase (CDK) inhibitors of the type [Fe(L(n))Cl(3)].nH(2)O (n=0 for 1, 1 for 2, 2 for 3-6; L(1)-L(6)=C2- and phenyl-substituted CDK inhibitors derived from 6-benzylamino-9-isopropylpurine), have been synthesized and characterized by elemental analysis, IR, (57)Fe Mössbauer, (1)H and (13)C NMR, and ES+ mass spectroscopies, conductivity and magnetic susceptibility measurements, and thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The study revealed that the compounds are mononuclear, tetrahedral high-spin (S=5/2) Fe(III) complexes with an admixture of an S=3/2 spin state originating probably from five-coordinated Fe(III) ions either connecting with a bidentate coordination mode of the CDK inhibitor ligand or relating to the possibility that one crystal water molecule enters the coordination sphere of the central atom in a portion of molecules of the appropriate complex. Nearly spin-only value of the effective magnetic moment (5.82micro(eff)/micro(B)) was determined for compound 1 due to absence of crystal water molecule(s) in the structure of the complex. Based on NMR data and DFT calculations, we assume that the appropriate organic ligand is coordinated to the Fe(III) ion through the N7 atom of a purine moiety. The cytotoxicity of the complexes was tested in vitro against selected human cancer cell lines (G-361, HOS, K-562 and MCF-7) along with the ability to inhibit the CDK2/cyclinE kinase. The best cytotoxicity (IC(50): 4-23muM) and inhibition activity (IC(50): 0.02-0.09microM) results have been achieved in the case of complexes 2-4, and complexes 3, 4 and 6, respectively. In addition, the X-ray structure of 2-chloro-6-benzylamino-9-isopropylpurine, i.e. a precursor for the preparation of L(1), L(4) and L(5), is also described.
Citace poskytuje Crossref.org
N-Benzyl-9-isopropyl-9H-purin-6-amine
2-Chloro-6-[(2,4-dimeth-oxy-benz-yl)amino]-9-isopropyl-9H-purine