Synthesis, Characterisation and In Vitro Anticancer Activity of Catalytically Active Indole-Based Half-Sandwich Complexes

Abstract

The synthesis, characterisation and evaluation of the in vitro cytotoxicity of four indole-based half-sandwich metal complexes towards two ovarian cancer cell lines (A2780 and A2780cisR) and one normal prostate cell line (PNT2) are presented herein. Although capable of inducing catalytic oxidation of NADH and able to reduce NAD+ with high turnover frequencies, in cells and in the presence of sodium formate, these complexes also strongly interact with biomolecules such as glutathione. This work highlights that efficient out-of-cells catalytic activity might lead to higher reactivity towards biomolecules, thus inhibiting the in-cells catalytic processes.

Indole-containing arene-ruthenium complexes with broad spectrum activity against antibiotic-resistant bacteria

“…Such shifts can be explained by the stereo-electronic effects due to the coordination to the metal moiety, as previously observed. ( Soldevila-Barreda et al., 2020 ) The signal for the NH proton is also no more visible after complexation, which confirms the successful synthesis of the complex.

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“…We have recently developed an interest in investigating the effect of bio-active indole moieties as bidentate ligands on the biological properties of half-sandwich metal complexes. ( Soldevila-Barreda et al., 2020 ) Indoles are bicyclic heterocycles that are commonly found in plants, bacteria and animals. Natural and synthetic indole-based compounds have been widely used as antibacterial, antifungal, anti-inflammatory, antihistaminic, and anticancer drugs.…”

Anticancer half-sandwich Ir(iii) complex and its interaction with various biomolecules and their mixtures – a case study with ascorbic acid

“…The effect of various biomolecules (including GSH or ASA) on the catalytic hydride transfer from NADH to various aldehydes was studied by Do and co-workers, 25 and others studied the reduction of NAD + in the presence of GSH. 54,55 Experiments using a cocktail of biomolecules allow more relevant correlation between the chemical ( e.g. , covalent interactions, catalysis) and biological ( e.g.…”

“…The effect of various biomolecules (including GSH or ASA) on the catalytic hydride transfer from NADH to various aldehydes was studied by Do and co-workers, 25 and others studied the reduction of NAD + in the presence of GSH. 54,55 Experiments using a cocktail of biomolecules allow more relevant correlation between the chemical (e.g., covalent interactions, catalysis) and biological (e.g., anticancer activity) properties of the new agents. Moreover, intracellular biomolecules are not isolated from each other in the cell, and their mutual interactions and relationship are usually well-described, as exemplified for ASA and GSH, or ASA and NADH, 56 i.e.…”

Fast Hydrolysis and Strongly Basic Water Adducts Lead to Potent Os(II) Half-Sandwich Anticancer Complexes

“…We expected that, albeit slowly, complexes 1−5 interacted with pure DMSO readily forming metal−DMSO adducts. 12,51 However, no significant changes were observed in the first 24 h for 2−5 in pure DMSO, while complex 1 was not totally unreactive toward DMSO, as it slowly evolved to form 1DMSO (22% conversion after 17 h) as determined by 1 H NMR (Figure 3A, black dots and diamonds for 1 and 2, respectively; Figure 3B, black triangles for 5). The different behavior of 1 at longer times is attributed to the higher tetherring tension, as the shorter tether arm generates a 5-membered tether ring (see the large C7 offset toward osmium in the X-ray structure of 1•1.5DCE, Figure 1 and Table S2), ultimately affording an Os−O bond more prone to dissociation.…”