Novel polyamide amidine anthraquinone platinum(II) complexes: cytotoxicity, cellular accumulation, and fluorescence distributions in 2D and 3D cell culture models
| Autor: | Nicole S. Bryce, Anthony T. S. Lo, Alice V. Klein, Trevor W. Hambley, Mathew H. Todd |
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| Rok vydání: | 2021 |
| Předmět: |
Nitrile
010405 organic chemistry Lexitropsin chemistry.chemical_element 010402 general chemistry 01 natural sciences Biochemistry Combinatorial chemistry Anthraquinone 0104 chemical sciences Inorganic Chemistry Amidine chemistry.chemical_compound chemistry Anthraquinones Cytotoxicity Platinum Pyrrole |
| Zdroj: | JBIC Journal of Biological Inorganic Chemistry. 26:217-233 |
| ISSN: | 1432-1327 0949-8257 |
| DOI: | 10.1007/s00775-020-01847-3 |
| Popis: | 1- and 1,5-Aminoalkylamine substituted anthraquinones (AAQs, 1C3 and 1,5C3) were peptide coupled to 1-, 2-, and 3-pyrrole lexitropsins to generate compounds that incorporated both DNA minor groove and intercalating moieties. The corresponding platinum(II) amidine complexes were synthesized through a synthetically facile amine-to-platinum mediated nitrile 'Click' reaction. The precursors as well as the corresponding platinum(II) complexes were biologically evaluated in 2D monolayer cells and 3D tumour cell models. Despite having cellular accumulation levels that were up to five-fold lower than that of cisplatin, the platinum complexes had cytotoxicities that were only three-fold lower. Accumulation was lowest for the complexes with two or three pyrrole groups, but the latter was the most active of the complexes exceeding the activity of cisplatin in the MDA-MB-231 cell line. All compounds showed moderate to good penetration into spheroids of DLD-1 cells with the distributions being consistent with active uptake of the pyrrole containing complexes in regions of the spheroids starved of nutrients. |
| Databáze: | OpenAIRE |
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