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

authors	Braga, SS; Marques, J; Heister, E; Diogo, CV; Oliveira, PJ; Paz, FAA; Santos, TM; Marques, MPM
nationality	International
journal	BIOMETALS
author keywords	Ruthenium complexes; 1,10-Phenanthroline-5,6-dione; Cyclodextrins; Cytotoxicity; Carbon nanotubes
keywords	PERMETHYLATED BETA-CYCLODEXTRIN; DRUG-DELIVERY; CARBON NANOTUBES; IN-VITRO; 1,10-PHENANTHROLINE-5,6-DIONE COMPLEXES; ANTIMICROBIAL ACTIVITY; H9C2 CARDIOMYOBLASTS; INCLUSION-COMPOUNDS; COLORIMETRIC ASSAY; X-RAY
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.
publisher	SPRINGER
issn	0966-0844
year published	2014
volume	27
issue	3
beginning page	507
ending page	525
digital object identifier (doi)	10.1007/s10534-014-9725-8
web of science category	Biochemistry & Molecular Biology
subject category	Biochemistry & Molecular Biology
unique article identifier	WOS:000335729900007
link	24652595