Antiproliferative activity of (η 6 -arene)ruthenacarborane sandwich complexes against HCT116 and MCF7 cell lines
2017
Аутори:
Gozzi, MartaSchwarze, Benedikt
Sárosi, Menyhárt-Botond
Lönnecke, Peter
Drača, Dijana
Maksimović-Ivanić, Danijela
Mijatović, Sanja
Hey-Hawkins, Evamarie
Тип документа:
Препринт (Рецензирана верзија)
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© The Royal Society of Chemistry 2017
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Приказ свих података о документуАпстракт:
Three [(η6-arene)RuC2B9H11] complexes (arene = p-cymene (2), biphenyl (3) and 1-Me-4-COOEt-C6H4 (4)) were synthesised according to modified literature procedures and fully characterised. 2–4 were found to be moderately active against two types of tumour cell lines (HCT116 and MCF7), with IC50 values in the low micromolar range. However, viability of normal, healthy cells (MRC-5 cell line, MLEC and mouse macrophages) was not affected by treatment with 2–4, indicating high selectivity of the metallacarborane complexes towards tumour cell lines, compared to the unselective antitumour agent cisplatin and other potential RuII drugs. Moreover, flow cytometric analysis suggested that 4 induces cell death via a caspase-dependent apoptotic mechanism. DFT calculations of the frontier molecular orbitals showed that the HOMO–LUMO gap in 2–4 is smaller than in the corresponding cyclopentadienyl complexes 2-Cp–4-Cp (e.g. 5.47 (2) vs. 6.31 eV (2-Cp)). In order to assess the stability of 2–4, particularly the ruthenium–dicarbollide bond, energy decomposition analysis (EDA) of 2–4, together with the respective cyclopentadienyl analogues 2-Cp–4-Cp, was performed. EDA suggests that the ruthenium(II)–dicarbollide bond in the three complexes is mostly ionic and far stronger than the ruthenium(II)–arene bond.
Извор:
Dalton Transactions, 2017Финансирање / пројекти:
- Молекуларни механизми физиолошке и фармаколошке контроле инфламације и канцера (RS-MESTD-Basic Research (BR or ON)-173013)
- Saxon State Ministry for Sciences and the Arts (SMWK)
- Funds of the Chemical Industry (VCI)
- Graduate School Leipzig School of Natural Sciences – Building with Molecules and Nano-objects (BuildMoNa)
DOI: 10.1039/C7DT02027A
PubMed: 28799598