Gold(I)-triphenylphosphine complexes with hypoxanthine-derived ligands: in vitro evaluations of anticancer and anti-inflammatory activities.

Abstract

A series of gold(I) complexes involving triphenylphosphine (PPh3) and one N-donor ligand derived from deprotonated mono- or disubstituted hypoxanthine (HLn) of the general composition [Au(Ln)(PPh3)] (1-9) is reported. The complexes were thoroughly characterized, including multinuclear high resolution NMR spectroscopy as well as single crystal X-ray analysis (for complexes 1 and 3). The complexes were screened for their in vitro cytotoxicity against human cancer cell lines MCF7 (breast carcinoma), HOS (osteosarcoma) and THP-1 (monocytic leukaemia), which identified the complexes 4-6 as the most promising representatives, who antiproliferative activity was further tested against A549 (lung adenocarcinoma), G-361 (melanoma), HeLa (cervical cancer), A2780 (ovarian carcinoma), A2780R (ovarian carcinoma resistant to cisplatin), 22Rv1 (prostate cancer) cell lines. Complexes 4-6 showed a significantly higher in vitro anticancer effect against the employed cancer cells, except for G-361, as compared with the commercially used anticancer drug cisplatin, with IC50 ≈ 1-30 µM. Anti-inflammatory activity was evaluated in vitro by the assessment of the ability of the complexes to modulate secretion of the pro-inflammatory cytokines, i.e. tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), in the lipopolysaccharide-activated macrophage-like THP-1 cell model. The results of this study identified the complexes as auspicious anti-inflammatory agents with similar or better activity as compared with the clinically applied gold-based antiarthritic drug Auranofin. In an effort to explore the possible mechanisms responsible for the biological effect, the products of interactions of selected complexes with sulfur-containing biomolecules (L-cysteine and reduced glutathione) were studied by means of the mass-spectrometry study.

• Authors: Radka Křikavová, Jan Hošek, Ján Vančo, Jakub Hutyra, Zdeněk Dvořák, Zdeněk Trávníček
• Journal: PloS one (PLoS One) Vol. 9 Issue 9 Pg. e107373 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25226034 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antineoplastic Agents
• Organophosphorus Compounds
• triphenylphosphine
• Hypoxanthine
• Gold

Topics

• Anti-Inflammatory Agents (chemistry, pharmacology, toxicity)
• Antineoplastic Agents (chemistry, pharmacology, toxicity)
• Cell Line
• Cell Line, Tumor
• Gold (chemistry)
• Humans
• Hypoxanthine (chemistry, pharmacology, toxicity)
• Macrophages (drug effects, metabolism)
• Models, Molecular
• Molecular Conformation
• Molecular Structure
• Nuclear Magnetic Resonance, Biomolecular
• Organophosphorus Compounds (chemistry, pharmacology, toxicity)