Gold(I)-Triphenylphosphine Complexes with Hypoxanthine-Derived Ligands: In Vitro Evaluations of Anticancer and Anti-Inflammatory Activities

PLoS One

Zdeněk Dvořák¹  Jan Hošek²  Jakub Hutyra²  Radka Křikavová²  Zdeněk Trávníček²  Ján Vančo² 

[1] Regional Centre of Advanced Technologies and Materials & Department of Cell Biology and Genetics, Faculty of Science, Palacký University, Olomouc, Czech Republic;Regional Centre of Advanced Technologies and Materials & Department of Inorganic Chemistry, Faculty of Science, Palacký University, Olomouc, Czech Republic

关键词: Cytotoxicity;    NMR spectroscopy;    Glutathione;    Crystal structure;    Secretion;    Cytokines;    Macrophages;    Single crystals;   

DOI  :  10.1371/journal.pone.0107373

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY