Structure–activity relations of Pd(II) and Pt(II) thiosemicarbazone complexes on different human glioblastoma cell lines
Please always quote using this URN: urn:nbn:de:bvb:20-opus-318281
- Ten thiosemicarbazone ligands obtained by condensation of pyridine-2-carbaldehyde, quinoline-2-carbaldehyde, 2-acetylpyridine, 2-acetylquinoline, or corresponding 2-pyridyl ketones with thiosemicarbazides RNHC(S)NHNH\(_{2}\) and R=CH\(_{3}\), C\(_{6}\)H\(_{5}\) were prepared in good yield. The reaction of [PdCl\(_{2}\)(cod)] with cod=1,5-cyclooctadiene or K\(_{2}\)[PtCl\(_{4}\)] resulted in a total of 17 Pd(II) and Pt(II) complexes isolated in excellent purity, as demonstrated by \(^{1}\)H, \(^{13}\)C, and, where applicable, \(^{195\)Pt NMRTen thiosemicarbazone ligands obtained by condensation of pyridine-2-carbaldehyde, quinoline-2-carbaldehyde, 2-acetylpyridine, 2-acetylquinoline, or corresponding 2-pyridyl ketones with thiosemicarbazides RNHC(S)NHNH\(_{2}\) and R=CH\(_{3}\), C\(_{6}\)H\(_{5}\) were prepared in good yield. The reaction of [PdCl\(_{2}\)(cod)] with cod=1,5-cyclooctadiene or K\(_{2}\)[PtCl\(_{4}\)] resulted in a total of 17 Pd(II) and Pt(II) complexes isolated in excellent purity, as demonstrated by \(^{1}\)H, \(^{13}\)C, and, where applicable, \(^{195\)Pt NMR spectroscopy combined with CHNS analysis. The cytotoxicity of the title compounds was studied on four human glioblastoma cell lines (GaMG, U87, U138, and U343). The most active compound, with a Pd(II) metal centre, a 2-quinolinyl ring, and methyl groups on both the proximal C and distal N atoms exhibited an EC\(_{50}\) value of 2.1 μM on the GaMG cell lines, thus being slightly more active than cisplatin (EC\(_{50}\) 3.4 μM) and significantly more potent than temozolomide (EC\(_{50}\) 67.1 μM). Surprisingly, the EC\(_{50}\) values were inversely correlated with the lipophilicity, as determined with the “shake-flask method”, and decreased with the length of the alkyl substituents (C\(_{1}\)>C\(_{8}\)>C\(_{10}\)). Correlation with the different structural motifs showed that for the most promising anticancer activity, a maximum of two aromatic rings (either quinolinyl or pyridyl plus phenyl) combined with one methyl group are favoured and the Pd(II) complexes are slightly more potent than their Pt(II) analogues.…
Author: | Ellina Schulz, Viviane Mawamba, Mario Löhr, Carsten Hagemann, Alexandra Friedrich, Ulrich Schatzschneider |
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URN: | urn:nbn:de:bvb:20-opus-318281 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Neurochirurgische Klinik und Poliklinik |
Fakultät für Chemie und Pharmazie / Institut für Anorganische Chemie | |
Language: | English |
Parent Title (English): | Zeitschrift für Anorganische und Allgemeine Chemie |
ISSN: | 0044-2313 |
Year of Completion: | 2022 |
Volume: | 648 |
Issue: | 12 |
Article Number: | e202200073 |
Source: | Zeitschrift für Anorganische und Allgemeine Chemie 2022, 648(12):e202200073. DOI: 10.1002/zaac.202200073 |
DOI: | https://doi.org/10.1002/zaac.202200073 |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 546 Anorganische Chemie |
Tag: | anticancer activity; glioblastoma; palladium; platinum; thiosemicarbazone |
Release Date: | 2023/07/05 |
Licence (German): | CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International |