Synthetic Strategies Towards O6‐Substituted Guanine Derivatives and Their Application in Medicine

Schirrmacher, Ralf; Schirrmacher, Esther; Muehlhausen, Ute; Kaina, Bernd; Waengler, Bjoern

doi:10.1002/chin.200611265

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“…In this work, we report a series of gold(I) complexes of the general formula [Au(L n )(PPh 3 )], where HL n represents variously mono- and disubstituted derivatives of hypoxanthine (See Figure 2 ). The rationale for the selection of these N -donor ligands is based on the fact that variously substituted derivatives of hypoxanthine have been identified as promising inhibitors of diverse essential enzymes, as cyclin-dependent kinases [19] , [20] and O 6-alkylguanine-DNA-alkyltransferase [21] , [22] , and therefore in combination with the {Au-PPh 3 } moiety could bring additional means of influencing the cellular metabolism both on the level of cell division, and modulation of cellular responses to the inflammatory stimuli.…”

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confidence: 99%

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

et al. 2014

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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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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Synthetic Strategies Towards O6‐Substituted Guanine Derivatives and Their Application in Medicine

Abstract: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Cited by 1 publication

References 1 publication

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

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

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