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Title: Carriers for metal complexes on tumour cells: the effect of cyclodextrins vs CNTs on the model guest phenanthroline-5,6-dione trithiacyclononane ruthenium(II) chloride
Author: Braga, Susana S.
Marques, Joana
Heister, Elena
Diogo, Catia V.
Oliveira, Paulo J.
Almeida Paz, Filipe A.
Santos, Teresa M.
Marques, Maria Paula M.
Issue Date: 2014
Publisher: SPRINGER
Abstract: The complex [Ru[9]aneS(3)(pdon)Cl]Cl (pdon = 1,10-phenanthroline-5,6-dione) was readily obtained from the stoichiometric reaction of Ru[9]aneS(3)(dmso)Cl-2 with pdon. Recrystallisation in ethanol using salicylic acid as a co-crystallisation helper afforded single-crystals suitable for the collection of X-ray diffraction data which afforded a reasonable structural description. Two different kinds of molecular carriers were tested as vehicles for this complex: carbon nanotubes (CNTs) and cyclodextrins. CNTs had an insufficient loading rate for the ruthenium complex at CNT concentrations deemed non-cytotoxic on cultured cells. The cyclodextrin (CD) carriers, beta-CD and TRIMEB (standing for permethylated beta-CD), were able to form two adducts, studied by powder X-ray diffraction, thermogravimetric analysis (TGA), C-13{H-1} CP/MAS NMR and FT-IR spectroscopies. The DNA thermal denaturation studies showed that the complex 1 is able to intercalate with DNA. The in vitro cytotoxicity of the free complex [Ru[9]aneS(3)(pdon)Cl]Cl (1) and of its two CD adducts (2 and 3) was assessed on both rodent and human cell lines. By using the mouse K1735-M2 melanoma cell line and the non-tumour rat H9c2 cardiomyoblasts, the results showed that 1 and 2 significantly inhibited the growth of the tumour cell line while displaying a good safety profile on cardiomyoblasts. Compound 3 at 100 mu M inhibited the proliferation of both cell lines, with a higher activity towards the melanoma cell line. The cytotoxicity of the compounds 1-3 was further assessed on human breast cancer cell lines. Against the MDA-MB-231 line, growth inhibition occurred only with 1 and 3 at the incubation time of 96 h, both with approximate inhibition rates of 50 %; against the MCF-7 line, mild cytotoxicity was observed at 48 h of incubation, with IC50 values calculated above 100 mu M for 1, 2 and 3.
Peer review: yes
DOI: 10.1007/s10534-014-9725-8
ISSN: 0966-0844
Publisher Version: 10.1007/s10534-014-9725-8
Appears in Collections:CICECO - Artigos

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