Novel octahedral Pt(IV) complex with di- n-propyl-( S,S)-ethylenediamine- N,N′-di-2-(3-cyclohexyl)propanoato ligand exerts potent immunomodulatory effects

• Published in: European journal of medicinal chemistry Vol. 47; no. 1; pp. 194 - 201
• Main Authors: Miljković, Djordje, Poljarević, Jelena M., Petković, Filip, Blaževski, Jana, Momčilović, Miljana, Nikolić, Ivana, Saksida, Tamara, Stošić-Grujičić, Stanislava, Grgurić-Šipka, Sanja, Sabo, Tibor J.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Masson SAS 2012; Elsevier
• Subjects: Animals; Bioinorganic chemistry; Biological and medical sciences; Cell Survival - drug effects; Cytokines; Cytotoxicity; Diamines - chemistry; Immunologic Factors - chemistry; Immunologic Factors - pharmacology; Immunology; Immunomodulators; Interferon-gamma - metabolism; Interleukin-17 - metabolism; Ligands; Lymph Nodes - cytology; Lymph Nodes - immunology; Medical sciences; Mice; Nitric Oxide - biosynthesis; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Peritoneum - drug effects; Peritoneum - metabolism; Pharmacology. Drug treatments; Platinum; Platinum - chemistry; Rats; Spleen - cytology; Spleen - immunology; Cytotoxicity; Immunology; Cytokines; Bioinorganic chemistry; Platinum; Cyclohexane derivatives; Ligand; Cytokine; Transition metal Complexes; Tetravalent metal Complexes; Enzyme immunoassay; Biological activity; Immunomodulator; Gene amplification; Platinum IV Complexes; Reverse transcription polymerase chain reaction; ELISA assay
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2011.10.042

We have recently reported that a novel octahedral Pt(IV) complex with di- n-propyl-( S,S)-ethylenediamine- N,N′-di-2-(3-cyclohexyl)propanoato ligand has a potent cytotoxic effect on glioma, melanoma and fibrosarcoma cell lines. In this work, we investigated the influence of the Pt(IV) compound on immune cells. We determined its effect on the viability of spleen cells and lymph node cells and on their capability to produce interferon (IFN)-γ and interleukin (IL)-17. Also, we researched the compound’s impact on peritoneal macrophages and generation of NO in these cells. Our results show that the complex has limited influence on cell viability of immune cells, but profound inhibitory effect on the production of examined immune mediators. These results are valuable as they show that the novel Pt(IV) complex applied in concentrations which are effective against tumor cells do not affect immune cell viability. Moreover, they also imply that the complex has immunomodulatory properties. [Display omitted] ► [Pt(L)Cl 4] inhibits tumor, but not immune cell viability. ► [Pt(L)Cl 4] inhibits cytokine and nitric oxide generation by immune cells. ► [Pt(L)Cl 4] has tumoricidal and immunomodulatory, but not immunosuppressive effect. ► These features promote [Pt(L)Cl 4] as a likely anticancer and immunomodulatory drug.