In vitro antitumor activity, metal uptake and reactivity with ascorbic acid and BSA of some gold(III) complexes with N,N′-ethylenediamine bidentate ester ligands
Authors/Creators
- 1. Department of Chemistry and Biochemistry, Faculty of Agriculture, University of Belgrade, Nemanjina 6, Belgrade, Zemun, Serbia
- 2. Department of Chemistry, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Studentski trg 14, 11000 Belgrade, Serbia.
- 3. Institute of Oncology and Radiology, 11000 Belgrade, Serbia.
- 4. Faculty of Agronomy, University of Kragujevac, Cara Dušana 34, 32000 Čačak, Serbia
- 5. Department of Chemistry Faculty of Science University of Kragujevac, R. Domanovica 12, P. O. Box 60, 34 000 Kragujevac, Serbia
- 6. Faculty of Chemistry, University of Belgrade, P.O. Box 158, 11001 Belgrade, Serbia.
- 7. Department of Bioorganic Chemistry, Leibniz-Institute of Plant Biochemistry, Weinberg 3, D 06120 Halle (Saale), Germany
Description
Four novel gold(III) complexes of general formulae [AuCl2{(S,S)-R2eddl}]PF6 (R2eddl =
O,O’-dialkyl-(S,S)-ethylenediamine-N,N’-di-2-(4-methyl)pentanoate, R = n-Pr, n-Bu, n-Pe, i-
Bu; 1–4, respectively), were synthesized and characterized by elemental analysis, UV/Vis,
IR, and NMR spectroscopy, as well as high resolution mass spectrometry. Density functional
theory calculations pointed out that (R,R)-N,N’-configuration diastereoisomers were
energetically the most favorable. Duo to high cytotoxic activity complex 3 was chosen for
stability study in DMSO, no decomposition occurs within 24h, and for the reaction with ascorbic acid in which was reduced immediately. Additionally, 3 interacts with bovine serum
albumin (BSA) as proven by UV/Vis spectroscopy. In vitro antitumor activity was
determined against human cervix adenocarcinoma (HeLa), human myelogenous leukemia
(K562), and human melanoma (Fem-x) cancer cell lines, as well as against non-cancerous
human embryonic lung fibroblast cells MRC-5. The highest activity was observed against
K562 cells (IC50: 5.04–6.51 μM). Selectivity indices showed that these complexes are less
toxic than cisplatin. 3 had a similar viability kinetics on HeLa cells as cisplatin. Drug
accumulation studies in HeLa cells showed that the total gold uptake increased much faster
than that of cisplatin pointing out that 3 more efficiently enters the cells than cisplatin.
Furthermore, morphological and cell cycle analysis reveal that gold(III) complexes induced
apoptosis in time- and dose-dependent manner.
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Additional details
Related works
- Is part of
- Journal article: 0162-0134 (ISSN)
Funding
- Ministry of Education, Science and Technological Development
- Synthesis, modeling, physicochemical and biological properties of organic compounds and related metal complexes 172016
- Ministry of Education, Science and Technological Development
- Rational design and synthesis of biologically active and coordination compounds and functional materials, relevant for (bio)nanotechnology 172035
- Ministry of Education, Science and Technological Development
- Biological response modifiers in physiological and pathological conditions 175011