Fullerenolates: metallated polyhydroxylated fullerenes with potent anti-amyloid activity

被引：55

作者：

Bobylev, A. G. ^{[2
]}

Kornev, A. B. ^{[1
]}

Bobyleva, L. G. ^{[2
]}

Shpagina, M. D. ^{[2
]}

Fadeeva, I. S. ^{[2
]}

Fadeev, R. S. ^{[2
]}

Deryabin, D. G. ^{[3
]}

Balzarini, J. ^{[4
]}

Troshin, P. A. ^{[1
]}

Podlubnaya, Z. A. ^{[2
,5
]}

机构：

[1] Russian Acad Sci, Inst Problems Chem Phys, Chernogolovka 142432, Moscow Region, Russia

[2] Russian Acad Sci, Inst Theoret & Expt Biophys, Pushchino 142290, Moscow Region, Russia

[3] Oregon State Univ, GSP, Orenburg 460018, Russia

[4] Katholieke Univ Leuven, Rega Inst Med Res, Lab Virol & Chemotherapy, B-3000 Louvain, Belgium

[5] Pushchino State Univ, Pushchino 142290, Moscow Region, Russia

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2011年 / 9卷 / 16期

基金：

俄罗斯基础研究基金会;

关键词：

ALZHEIMERS-DISEASE; THIOFLAVIN-T; BINDING;

D O I：

10.1039/c1ob05067b

中图分类号：

O62 [有机化学];

学科分类号：

070303 [有机化学];

摘要：

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 A beta(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.

引用

页码：5714 / 5719

页数：6

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