Fullerenolates: metallated polyhydroxylated fullerenes with potent anti-amyloid activity

• Published in: Organic & biomolecular chemistry 2011-08, Vol.9 (16), p.5714
• Main Authors: Bobylev, A G, Kornev, A B, Bobyleva, L G, Shpagina, M D, Fadeeva, I S, Fadeev, R S, Deryabin, D G, Balzarini, J, Troshin, P A, Podlubnaya, Z A
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - drug therapy; Amyloid beta-Peptides - antagonists & inhibitors; Amyloid beta-Peptides - metabolism; Amyloidosis - drug therapy; Animals; Brain - drug effects; Brain - metabolism; Cell Line; Cell Survival - drug effects; Fullerenes - chemistry; Fullerenes - pharmacology; Fullerenes - toxicity; Humans; Mice; Peptide Fragments - antagonists & inhibitors; Peptide Fragments - metabolism
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c1ob05067b

It has been revealed for the first time that sodium fullerenolate Na(4)[C(60)(OH)(∼30)] (NaFL), a water soluble polyhydroxylated [60]fullerene derivative, destroys amyloid fibrils of the Aβ(1-42) peptide in the brain and prevents their formation in in vitro experiments. The cytotoxicity of NaFL was found to be negligibly low with respect to nine different culture cell lines. At the same time, NaFL showed a very low acute toxicity in vivo. The maximal tolerable dose (MTD) and LD50 for NaFL correspond to 1000 mg kg(-1) and 1800 mg kg(-1), respectively, as revealed by in vivo tests in mice using intraperitoneal drug injection. The observed pronounced anti-amyloid activity and low toxicity of NaFL make it a very promising lead drug for the development of potent fullerene-based therapeutic approaches for the treatment of amyloidoses, such as Alzheimer's disease and others.