Influence of methoxy groups on the antiproliferative effects of [Fe(III)(salophene-OMe)Cl] complexes.
We synthesized methoxy-substituted iron(III)-salophene complexes ([Fe(III)(OMe-salophene)Cl] with salophene = N,N'-bis(salicylidene)-1,2-phenylenediamine) and analyzed their biological activity in MCF-7 and MDA-MB-231 breast cancer as well as in HT-29 colon carcinoma cells. The results obtained in a time-dependent chemosensitivity test clearly demonstrated the correlation between the cytotoxicity of the complexes and the position of methoxy substituents in the salicylidene moieties: 3-OCH(3) (4) < 5-OCH(3) (8) < H (2) < 4-OCH(3) (6) = 6-OCH(3) (10). Compounds 6 and 10 caused cytocidal effects already at a concentration of 0.5 μM. Both lead compound 2 and complex 8 showed similar time response curves, however, with a 5-fold lower activity compared to 6 and 10, respectively. Referring to [Fe(III)(salophene)Cl] (2), methoxy substitution was accompanied with the loss of tumor cell selectivity. Moreover, the free ligands (1, 3, 5, 7, and 9) were inactive.
Hille
Annegret
A
Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Strasse 2 + 4, D-14195 Berlin, Germany.
Gust
Ronald
R
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005290:Ferric Compounds / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D012459:Salicylates / Q000737:chemistry / Q000494:pharmacology*
D005290:Ferric Compounds; D012459:Salicylates; C090416:salophen