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.
Highlights
Gold-based medication was used for a wide range of ailments already in the distant history of ancient China 2500 BC [1,2]
General Properties of the Au(I) complexes This work reports on the preparation, thorough characterization, and in vitro cytotoxic and anti-inflammatory activities of a series of gold(I)-triphenylphosphine complexes [Au(L1–9)(PPh3)] involving mono- or disubstituted derivatives of hypoxanthine
The results of the in vitro cytotoxic activity testing of 1–9 and cisplatin against human breast adenocarcinoma (MCF7) and osteosarcoma (HOS): cells were treated with the tested compounds for 24 h; measurements were performed in triplicate, and cytotoxicity experiment was repeated in three different cell passages; data are expressed as IC506SE. aadopted from Ref. [42]; n.d. – not determined. doi:10.1371/journal.pone.0107373.t002
Summary
Gold-based medication was used for a wide range of ailments already in the distant history of ancient China 2500 BC [1,2]. General Properties of the Au(I) complexes This work reports on the preparation, thorough characterization, and in vitro cytotoxic and anti-inflammatory activities of a series of gold(I)-triphenylphosphine complexes [Au(L1–9)(PPh3)] involving mono- or disubstituted derivatives of hypoxanthine
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