Novel iron complexes bearing N6-substituted adenosine derivatives: Synthesis, magnetic, Fe-57 Mossbauer, DFT, and in vitro cytotoxicity studies

0325895 - ÚEB 2009 RIV GB eng J - Journal Article
Trávníček, Zdeněk - Mikulík, J. - Čajan, Michal - Zbořil, R. - Popa, Igor
Novel iron complexes bearing N6-substituted adenosine derivatives: Synthesis, magnetic, Fe-57 Mossbauer, DFT, and in vitro cytotoxicity studies.
[Novel iron complexes bearing N6-substituted adenosine derivatives: Synthesis, magnetic, Fe-57 Mossbauer, DFT, and in vitro cytotoxicity studies.]
Bioorganic & Medicinal Chemistry. Roč. 16, č. 18 (2008), s. 8719-8728. ISSN 0968-0896. E-ISSN 1464-3391
Institutional research plan: CEZ:AV0Z50380511
Keywords : iron complexes * adenosine derivatives * Fe-57 Mossbauer spectroscopy
Subject RIV: CE - Biochemistry
Impact factor: 3.075, year: 2008

Iron complexes (1-7) involving N6-benzyladenosine derivatives of the predominant composition [Fe(L-n)Cl-3]center dot H2O {where L-1 = N6-(2-fluorobenzyl)adenosine (1), L-2 = N6-(4-fluorobenzyl)adenosine (2), L-3 = N6-(2-trifluoromethylbenzyl)adenosine (3), L-4 = N6-(3-trifluoromethylbenzyl)adenosine (4), L-5 = N6-(4-trifluoromethylbenzyl)adenosine (5), L-6 = N6-(4-trifluoromethoxybenzyl)adenosine (6), and L-7 = N6-(4-chlorobenzyl)adenosine (7)} have been synthesized. The compounds have been characterized by elemental analysis, variable-temperature and in-field Fe-57 Mossbauer, ES+ MS, FTIR, H-1 and C-13 NMR spectroscopies, magnetochemical and conductivity measurements, thermal (TGA/DSC/DTA) analyses, and DFT calculations. It has been found that the organic molecule is coordinated to iron via N7 atom of the appropriate adenosine derivative and the products are represented by mixtures of complexes with various iron oxidation (Fe-III/Fe-II) and spin states (S = 5/2, 4/2, 3/2, 2/2) and geometries (tetrahedral or trigonal bipyramidal). It is caused by the fact that partial redox processes proceed during the reactions due to the presence of a ribose moiety, which is oxidized to the corresponding 5'-ribotic acid, and simultaneously, a portion of Fe-III cations is reduced to Fe-II ones. Moreover, a significant effect of crystal water molecules on stereochemistry, and hence, on magnetic and spectral properties of the prepared complexes has been found. The compounds have been tested for their in vitro cytotoxicity against the following human cancer cell lines: malignant melanoma (G-361), osteogenic sarcoma (HOS), chronic myelogenous leukemia (K-562), and breast adenocarcinoma (MCF-7). The most important results have been obtained for complex 2 with IC50 values 8-16 mu M against HOS, K-562, and MCF-7 cell lines, and for complex 6 with IC50 value 4 mu M against MCF-7 cell line.

Novel iron complexes bearing N6-substituted adenosine derivatives: Synthesis, magnetic, Fe-57 Mossbauer, DFT, and in vitro cytotoxicity studies.
Permanent Link: http://hdl.handle.net/11104/0173176