title: Fluorinated Fe(III) salophene complexes: optimization of tumor cell specific activity and utilization of fluorine labeling for in vitro analysis.
abstract: Fluorine-substituted iron(III) salophene complexes (salophene = N,N'-bis(salicylidene)-1,2-phenylenediamine) were synthesized and evaluated for biological activity. All complexes showed growth inhibitory effects with IC50 values ranging from 0.05 to 2.45 μM against HT-29 colon carcinoma as well as MCF-7 and MDA-MB-231 mammary carcinoma cells (cisplatin: 5.75, 12.72, 5.81 μM, respectively). HR-CS MAS investigations revealed that the complexes were highly protein-bound already after an incubation period of 10 min and accumulated more effectively in tumor cells than cisplatin. Interestingly, the ligands were enriched in the cells too, indicating that the salophene moiety acts as a carrier ligand and mediates the uptake of the complexes. Furthermore, induction of apoptosis proved to be dependent on the substitution pattern as well as on the tumor cell line, as evidenced from the annexin V-FITC/PI assay. Most of the complexes, especially the highly active 5-Fe, showed tumor cell specific effects and no/less influence on the proliferation of T-cells generated from the peripheral blood of healthy individuals.
authors.affiliation: Department of Pharmaceutical Chemistry, Institute of Pharmacy, Center for Molecular Biosciences Innsbruck, CCB-Centrum for Chemistry and Biomedicine, Universität Innsbruck , Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Irene
authors.initials: I
authors.lastname: Würtenberger
authors.forename: Valeria
authors.initials: V
authors.lastname: Follia
authors.forename: Fanni
authors.initials: F
authors.lastname: Lerch
authors.forename: Christiane
authors.initials: C
authors.lastname: Cwikla
authors.forename: Nathalie
authors.initials: N
authors.lastname: Fahrner
authors.forename: Christina
authors.initials: C
authors.lastname: Kalchschmidt
authors.forename: Brigitte
authors.initials: B
authors.lastname: Flögel
authors.forename: Brigitte
authors.initials: B
authors.lastname: Kircher
authors.forename: Ronald
authors.initials: R
authors.lastname: Gust
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D005290:Ferric Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D005461:Fluorine; D006801:Humans; D012459:Salicylates / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D005290:Ferric Compounds; D012459:Salicylates; C090416:salophen; D005461:Fluorine; D004247:DNA