Interaction with Blood Proteins of a Ruthenium(II) Nitrofuryl Semicarbazone Complex: Effect on the Antitumoral Activity.
The steady rise in the cancer burden and grim statistics set a vital need for new therapeutic solutions. Given their high efficiency, metallodrugs are quite appealing in cancer chemotherapy. This work examined the anticancer activity of an anti-trypanosomal ruthenium-based compound bearing the 5-nitrofuryl pharmacophore, [RuII(dmso)2(5-nitro-2-furaldehyde semicarbazone)] (abbreviated as RuNTF; dmso is the dimethyl sulfoxide ligand). The cytotoxicity of RuNTF was evaluated in vitro against ovarian adenocarcinoma, hormone-dependent breast adenocarcinoma, prostate carcinoma (grade IV) and V79 lung fibroblasts human cells. The activity of RuNTF was similar to the benchmark metallodrug cisplatin for the breast line and inactive against the prostate line and lung fibroblasts. Given the known role of serum protein binding in drug bioavailability and the distribution via blood plasma, this study assessed the interaction of RuNTF with human serum albumin (HSA) by circular dichroism (CD) and fluorescence spectroscopy. The fluorescence emission quenching from the HSA-Trp214 residue and the lifetime data upon RuNTF binding evidenced the formation of a 1:1 {RuNTF-albumin} adduct with log Ksv = (4.58 ± 0.01) and log KB = (4.55 ± 0.01). This is supported by CD data with an induced CD broad band observed at ~450 nm even after short incubation times. Importantly, the binding to either HSA or human apo-transferrin is beneficial to the cytotoxicity of the complex towards human cancer cells by enhancing the cytotoxic activity of RuNTF.
['Demoro|Bruno|B|', 'Bento-Oliveira|Andreia|A|', 'Marques|Fernanda|F|', 'Costa Pessoa|João|J|0000-0002-3978-9964', 'Otero|Lucía|L|', 'Gambino|Dinorah|D|0000-0001-8678-7374', 'F M de Almeida|Rodrigo|R|', 'Tomaz|Ana Isabel|AI|0000-0002-2249-4684']
D000465:Algorithms D000970:Antineoplastic Agents D001798:Blood Proteins D002942:Circular Dichroism D056831:Coordination Complexes D004347:Drug Interactions D006801:Humans D008958:Models, Molecular D008962:Models, Theoretical D015394:Molecular Structure D011485:Protein Binding D012428:Ruthenium D012664:Semicarbazones D000075462:Serum Albumin, Human
ruthenium(II) cancer cytotoxicity human serum albumin circular dichroism fluorescence 5-nitrofurylsemicarbazone conditional binding constants human serum apo-transferrin. plasma protein binding