title: 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.affiliation: Regional Centre of Advanced Technologies and Materials & Department of Inorganic Chemistry, Faculty of Science, Palacký University, Olomouc, Czech Republic.
authors.forename: Radka
authors.initials: R
authors.lastname: Křikavová
authors.affiliation: Regional Centre of Advanced Technologies and Materials & Department of Inorganic Chemistry, Faculty of Science, Palacký University, Olomouc, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Hošek
authors.affiliation: Regional Centre of Advanced Technologies and Materials & Department of Inorganic Chemistry, Faculty of Science, Palacký University, Olomouc, Czech Republic.
authors.forename: Ján
authors.initials: J
authors.lastname: Vančo
authors.affiliation: Regional Centre of Advanced Technologies and Materials & Department of Inorganic Chemistry, Faculty of Science, Palacký University, Olomouc, Czech Republic.
authors.forename: Jakub
authors.initials: J
authors.lastname: Hutyra
authors.affiliation: Regional Centre of Advanced Technologies and Materials & Department of Cell Biology and Genetics, Faculty of Science, Palacký University, Olomouc, Czech Republic.
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Dvořák
authors.affiliation: Regional Centre of Advanced Technologies and Materials & Department of Inorganic Chemistry, Faculty of Science, Palacký University, Olomouc, Czech Republic.
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Trávníček
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D045744:Cell Line, Tumor; D006046:Gold / Q000737:chemistry*; D006801:Humans; D019271:Hypoxanthine / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D009943:Organophosphorus Compounds; C061896:triphenylphosphine; D019271:Hypoxanthine; D006046:Gold