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

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 19; p. 4540
• Main Authors: Soldevila-Barreda, Joan J, Fawibe, Kehinde B, Azmanova, Maria, Rafols, Laia, Pitto-Barry, Anaïs, Eke, Uche B, Barry, Nicolas P E
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.10.2020; MDPI
• Subjects: anticancer; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor activity; bioinorganic chemistry; Biomolecules; Cancer therapies; Catalysis; Catalytic activity; catalytic drugs; Cell Line, Tumor; Cell Survival - drug effects; Cisplatin - pharmacology; Cytotoxicity; Gene expression; Glutathione - chemistry; half-sandwich complexes; Homeostasis; Humans; Hydrogenation; Indole; Indoles; Indoles - chemical synthesis; Indoles - chemistry; Indoles - pharmacology; Inhibitory Concentration 50; Kinetics; Ligands; Metabolism; Metal complexes; Metals; Molecular Conformation; NAD - chemistry; NADH; Nicotinamide adenine dinucleotide; Ovarian cancer; Oxidation; Oxidative stress; Prostate; Proton Magnetic Resonance Spectroscopy; Silver; Solutions; Spectrophotometry, Ultraviolet; Tumor cell lines; half-sandwich complexes; catalytic drugs; Indole; anticancer; bioinorganic chemistry
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25194540

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.