Interaction with Blood Proteins of a Ruthenium(II) Nitrofuryl Semicarbazone Complex: Effect on the Antitumoral Activity

Abstract

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.

Insight into the interaction between tannin acid and bovine serum albumin from a spectroscopic and molecular docking perspective

“…There was a wave peak of BSA around 342 nm, which indicated that the tryptophan residue was the main source of BSA uorescence intensity. 27 When TA was added, the uorescence intensity of BSA decreased signicantly, which indicated that TA had a uorescence quenching effect on BSA, and the quenching effect had a strong dependence on the amount of TA added. In addition, the uorescence spectrum of BSA shied slightly red from 342.0 nm to 345.2 nm with a gradual increase in TA concentration.…”

Biophysicochemical studies of a ruthenium (II) nitrosyl thioether‐thiolate complex binding to BSA: Mechanistic information, molecular docking, and relationship to antibacterial and cytotoxic activities

“…[14] Albumin is the most abundant protein in the plasma [15] and the major nonspecific transporter in the blood. [16] The primary and secondary structures of albumin have been studied previously. [17] BSA is one of the most researched proteins, having activities that are critical for the disposition and transportation of a wide range of substances inside the body, including metal ions, medicines, hormones, steroids, and fatty acids.…”

Alkyne Functionalization of a Photoactivated Ruthenium Polypyridyl Complex for Click-Enabled Serum Albumin Interaction Studies

“…Common methods to investigate metallodrug–protein interactions are X-ray diffraction analysis, ,, electrospray ionization mass spectrometry (ESI-MS), , inductively coupled plasma optical emission spectrometry (ICP-OES) or mass spectrometry (ICP-MS), UV–vis spectroscopy, circular dichroism (CD) spectroscopy, tryptophan fluorescence spectroscopy, − (nano)­liquid chromatography, , gel electrophoresis, − capillary electrophoresis , or NMR. − For emissive metallodrugs, the metal complex and hence its interaction with biomolecules can be imaged on gel electrophoresis or in cells by emission microscopy. , For the nonemissive metallodrugs considered here, however, this approach is ineffective. In organic chemical biology a well-developed method to visualize interaction between proteins and nonemissive organic inhibitors is based on bioorthogonal chemistry .…”