Synthesis and In Vitro Pharmacological Behavior of Platinum(II) Complexes Containing 1,2-Diamino-1-(4-fluorophenyl)-2-alkanol Ligands

In continuation of our effort to optimize the pharmacological profile of [1,2-diamino-1,2-bis­(4-fluorophenyl)­ethane]­dichloridoplatinum­(II) complexes, we synthesized [1,2-diamino-1-(4-fluorophenyl)­alkanol]­dichloridoplatinum­(II) analogs. The aim of this study was to evaluate the influence of hydroxyl groups at the C2 moiety on aqueous solubility, lipophilicity, cellular platinum accumulation, and cytotoxicity against MDA-MB-231, U-937, RAJI, and SC-1 cells as well as against cisplatin-sensitive and cisplatin-resistant A2780 and A2780cisR ovarian carcinoma cells. As expected, the OH groups improved the water solubility and decreased the lipophilicity of the neutral ligands, resulting in complexes with favorable pharmacokinetic properties. The cellular uptake of the compounds in MDA-MB-231 and U-937 cells proved to depend on the configuration and showed only a slight correlation with lipophilicity. The most active complexes were <i>R</i>,<i>R</i>/<i>S</i>,<i>S</i> configured, which points to a carrier-mediated mode of action. [<i>threo</i>-1,2-Diamino-1-(4-fluorophenyl)­propan]­dichloridoplatinum­(II) and [<i>threo</i>-2,3-diamino-3-(4-fluorophenyl)­propan-1-ol]­dichloridoplatinum­(II) possessed only low cross-resistance to cisplatin and were up to 10-fold more active in lymphoma cell lines

Fluorinated Fe(III) Salophene Complexes: Optimization of Tumor Cell Specific Activity and Utilization of Fluorine Labeling for in Vitro Analysis

Fluorine-substituted iron­(III) salophene complexes (salophene = <i>N</i>,<i>N</i>′-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 <b>5-Fe</b>, showed tumor cell specific effects and no/less influence on the proliferation of T-cells generated from the peripheral blood of healthy individuals

Correction to “Development of Cytotoxic GW7604-Zeise’s Salt Conjugates as Multitarget Compounds with Selectivity for Estrogen Receptor-Positive Tumor Cells”

Correction to “Development of Cytotoxic GW7604-Zeise’s Salt Conjugates as Multitarget Compounds with Selectivity for Estrogen Receptor-Positive Tumor Cells