Biomedical properties of a series of ruthenium-N-heterocyclic carbene complexes based on oxidant activity in vitro and assessment in vivo of biosafety in zebrafish embryos.
N-Heterocyclic carbene (NHC) ligands have attracted great interest over the last decade for their use in the design of homogenous catalysts. NHC-based metal complexes have interesting potential biomedical applications, such as in antimicrobial and cancer therapy, which are beginning to be explored more fully. We have studied here the oxidant activities of a series of Ru(II) complexes in vitro and zebrafish (Danio rerio) have been used as a model in vivo to investigate and characterize the toxicity of some of these compounds. Dual behavior was observed for the NHC-based complexes as they behaved as antioxidants at low concentrations but showed pro-oxidant capacity at higher concentrations. Zebrafish embryos were exposed to Ru(II) complexes under several different conditions (0 or 24 h postfertilization, with or without the chorion) and various parameters, such as viability, edema, heart rate, blood coagulation, pigmentation, scoliosis, malformation, and hatching, were tested. In general, zebrafish embryos were not harmed by exposure to Ru(II) complexes whatever the experimental conditions. Several toxicity profiles were observed depending upon the chemical structure of the compound in question. Their characteristics as pro-oxidant and/or antioxidant agents together with their biosafety may point to their having biomedical applications as antitumoral or neuroprotective drugs.
Alfaro
Juan M
JM
BioPharma Unit, Neuron BPh, Health Science Technology Park, Armilla, Spain.
Prades
Amparo
A
del Carmen Ramos
María
M
Peris
Eduardo
E
Ripoll-Gómez
Jorge
J
Poyatos
Macarena
M
Burgos
Javier S
JS
D000818:Animals; D006321:Heart / Q000187:drug effects / Q000196:embryology; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000633:toxicity*; D007814:Larva / Q000187:drug effects; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D015394:Molecular Structure; D016877:Oxidants / Q000737:chemistry / Q000633:toxicity*; D017975:Ruthenium Compounds / Q000737:chemistry / Q000633:toxicity*; D013329:Structure-Activity Relationship; D015027:Zebrafish / Q000196:embryology*
D006571:Heterocyclic Compounds; D016877:Oxidants; D017975:Ruthenium Compounds; C030011:carbene; D008697:Methane