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.
abstract: The complex [Ru[9]aneS3(pdon)Cl]Cl (pdon = 1,10-phenanthroline-5,6-dione) was readily obtained from the stoichiometric reaction of Ru[9]aneS3(dmso)Cl2 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, β-CD and TRIMEB (standing for permethylated β-CD), were able to form two adducts, studied by powder X-ray diffraction, thermogravimetric analysis (TGA), (13)C{(1)H} 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]aneS3(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 μM 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 μM for 1, 2 and 3.
authors.affiliation: Department of Chemistry, QOPNA Research Unit, University of Aveiro, 3810-193, Aveiro, Portugal, sbraga@ua.pt.
authors.forename: Susana S
authors.initials: SS
authors.lastname: Braga
authors.forename: Joana
authors.initials: J
authors.lastname: Marques
authors.forename: Elena
authors.initials: E
authors.lastname: Heister
authors.forename: Cátia V
authors.initials: CV
authors.lastname: Diogo
authors.forename: Paulo J
authors.initials: PJ
authors.lastname: Oliveira
authors.forename: Filipe A Almeida
authors.initials: FA
authors.lastname: Paz
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Santos
authors.forename: Maria Paula M
authors.initials: MP
authors.lastname: Marques
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D003505:Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D008545:Melanoma; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D032386:Myoblasts, Cardiac / Q000187:drug effects; D053769:Nanocapsules / Q000737:chemistry; D037742:Nanotubes, Carbon / Q000737:chemistry*; D033362:Powder Diffraction; D051381:Rats; D013818:Thermogravimetry; D044366:Transition Temperature
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D003505:Cyclodextrins; D004337:Drug Carriers; D053769:Nanocapsules; D037742:Nanotubes, Carbon; C000594168:phenanthroline-5,6-dione trithiacyclononane ruthenium(II); D004247:DNA; C427203:calf thymus DNA