Neurodegenerative diseases are often associated with
an uncontrolled
amyloid aggregation. Hence, many studies are oriented to discover
new compounds that are able to modulate self-recognition mechanisms
of proteins involved in the development of these pathologies. Herein,
three metal-complexes able to release carbon monoxide (CORMs) were
analyzed for their ability to affect the self-aggregation of the amyloidogenic
fragment of nucleophosmin 1, corresponding to the second helix of
the three-helix bundle located in the C-terminal domain of the protein,
i.e., NPM1264–277, peptide. These complexes were
two cymantrenes coordinated to the nucleobase adenine (Cym-Ade) and to the antibiotic ciprofloxacin (Cym-Cipro) and
a Re(I)-compound containing 1,10-phenanthroline and 3-CCCH2NHCOCH2CH2-6-bromo-chromone as ligands (Re-Flavo). Thioflavin T (ThT) assay, UV–vis absorption
and fluorescence spectroscopies, scanning electron microscopy (SEM),
and electrospray ionization mass spectrometry (ESI-MS) indicated that
the three compounds have different effects on the peptide aggregation.Cym-AdeandCym-Ciproact as aggregating agents.Cym-Adeinduces the formation of NPM1264–277fibers longer and stiffer than that formed by NPM1264–277alone; irradiation of complexes speeds the formation of fibers that
are more flexible and thicker than those found without irradiation.Cym-Ciproinduces the formation of longer fibers, although
slightly thinner in diameter. Conversely,Re-Flavoacts
as an antiaggregating agent. Overall, these results indicate that
metal-based CORMs with diverse structural features can have a different
effect on the formation of amyloid fibers. A proper choice of ligands
attached to metal can allow the development of metal-based drugs with
potential application as antiamyloidogenic agents.