Abstract |
The gold(I) mixed- ligand complexes involving O-substituted derivatives of 9-deazahypoxanthine (HLn) and triphenylphosphine (PPh3) with the general formula [Au(Ln)(PPh3)] (1-5) were prepared and thoroughly characterized by elemental analysis, FT-IR and multinuclear NMR spectroscopy, ESI+ mass spectrometry, single crystal X-ray (HL5 and complex 2) and TG/DTA analyses. Complexes 1-5 were evaluated for their in vitro antitumor activity against nine human cancer lines, i.e. MCF7 ( breast carcinoma), HOS ( osteosarcoma), A549 ( adenocarcinoma), G361 ( melanoma), HeLa ( cervical cancer), A2780 (ovarian carcinoma), A2780R (ovarian carcinoma resistant to cisplatin), 22Rv1 ( prostate cancer) and THP-1 (monocytic leukaemia), for their in vitro anti-inflammatory activity using a model of LPS-activated macrophages, and for their in vivo antiedematous activity by λ- carrageenan-induced hind paw edema model on rats. The results showed that the complexes 1-5 exhibit selective in vitro cytotoxicity against MCF7, HOS, 22Rv1, A2780 and A2780R, with submicromolar IC50 values for 2 against the MCF7 (0.6 µM) and HOS (0.9 µM). The results of in vitro cytotoxicity screening on primary culture of human hepatocytes (HEP220) revealed up to 30-times lower toxicity of compounds against healthy cells as compared with cancer cells. Additionally, the complexes 1-5 significantly influence the secretion and expression of pro-inflammatory cytokines TNF-α and IL-1β by a similar manner as a commercially used anti-arthritic drug Auranofin. The tested complexes also significantly influence the rate and overall volume of the edema, caused by the intraplantar application of λ- carrageenan polysaccharide to rats. Based on these promising results, the presented compounds could qualify to become feasible candidates for advanced testing as potential antitumor and anti-inflammatory drug-like compounds.
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Authors | Ján Vančo, Jana Gáliková, Jan Hošek, Zdeněk Dvořák, Lenka Paráková, Zdeněk Trávníček |
Journal | PloS one
(PLoS One)
Vol. 9
Issue 10
Pg. e109901
( 2014)
ISSN: 1932-6203 [Electronic] United States |
PMID | 25333949
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 9-deazahypoxanthine
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Hypoxanthines
- Gold
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Topics |
- Animals
- Anti-Inflammatory Agents
(chemistry, pharmacology, therapeutic use)
- Antineoplastic Agents
(chemistry, pharmacology, therapeutic use)
- Cell Line, Tumor
- Disease Models, Animal
- Edema
(drug therapy)
- Gold
(chemistry, pharmacology, therapeutic use)
- Hepatocytes
(drug effects)
- Humans
- Hypoxanthines
(chemistry, pharmacology, therapeutic use)
- Inflammation
(drug therapy)
- Neoplasms
(drug therapy)
- Rats
- Spectroscopy, Fourier Transform Infrared
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