Inhibition of the HIV-1 protease by fullerene derivatives: model building studies and experimental verification

Friedman, Simon H.; DeCamp, Dianne L.; Sijbesma, Rint P.; Srdanov, G.; Wudl, Fred; Kenyon, George L.

doi:10.1021/ja00068a005

Cited by 936 publications

(551 citation statements)

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“…They have also exhibited antitumor and antiviral activity, including inhibition of HIV protease (Bogdanovic et al, 2004;Friedman et al, 1993;Nakamura and Isobe, 2003;Schinazi et al, 1993). Although the water-soluble fullerenes are not genotoxic (Zakharenko et al, 1997) they are retained in the body for long periods, raising concerns about chronic toxic effects (Yamago et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Phototoxicity and cytotoxicity of fullerol in human lens epithelial cells

Roberts

Wielgus

Boyes

et al. 2008

Toxicology and Applied Pharmacology

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The water-soluble, hydroxylated fullerene [fullerol, nano-C 60 (OH) [22][23][24][25][26] ] has several clinical applications including use as a drug carrier to bypass the blood ocular barriers. We have assessed fullerol's potential ocular toxicity by measuring its cytotoxicity and phototoxicity induced by UVA and visible light in vitro with human lens epithelial cells (HLE B-3). Accumulation of nano-C 60 (OH) [22][23][24][25][26] in the cells was confirmed spectrophotometrically at 405 nm and cell viability estimated using MTS and LDH assays. Fullerol was cytotoxic to HLE B-3 cells maintained in the dark at concentrations higher than 20 µM. Exposure to either UVA or visible light in the presence of >5 µM fullerol induced phototoxic damage. When cells were pretreated with non-toxic antioxidants: 20 µM lutein, 1 mM N-acetyl cysteine, or 1 mM L-ascorbic acid prior to irradiation, only the singlet oxygen quencher lutein significantly protected against fullerol photodamage. Apoptosis was observed in lens cells treated with fullerol whether or not the cells were irradiated, in the order UVA > visible light > dark. Dynamic light scattering (DLS) showed that in the presence of the endogenous lens protein α-crystallin, large aggregates of fullerol were reduced. In conclusion, fullerol is both cytotoxic and phototoxic to human lens epithelial cells. Although the acute toxicity of water soluble nano-C 60 (OH) 22-26 is low, these compounds are retained in the body for long periods, raising concern for their chronic toxic effect. Before fullerols are used to deliver drugs to the eye, they should be tested for photo-and cytotoxicity in vivo.

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Section: Introductionmentioning

confidence: 99%

Phototoxicity and cytotoxicity of fullerol in human lens epithelial cells

Roberts

Wielgus

Boyes

et al. 2008

Toxicology and Applied Pharmacology

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“…2 All these properties have been exploited in the fabrication of pioneering organic photovoltaic devices 3 as well as in the construction of supramolecular architectures. 4 In addition, fullerene and its derivatives exhibit satisfactory enzyme-inhibiting, 5 radical quenching, 6 and DNA-cleavage abilities. 7 On the other hand, cyclodextrins (CDs) represent one of the most studied molecular receptors in the field of supramolecular chemistry due to their capability to include various guest molecules in the hydrophobic cavity.…”

Section: Introductionmentioning

confidence: 99%

Cyclodextrin-[60]fullerene conjugates: synthesis, characterization, and electrochemical behavior

Giacalone¹,

D’Anna²,

Giacalone³

et al. 2006

Tetrahedron Letters

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Abstract-Three different functionalized b-cyclodextrins (b-CDs) bearing the C 60 moiety linked covalently have been prepared in good yields by reaction between the parent b-CD and [60]fullerene via 1,3-dipolar cycloaddition. These compounds have been fully spectroscopically characterized and their electrochemical behavior has been investigated. Surprisingly, the electrochemical properties of the C 60 cage remain unaltered even after chemical functionalization, making these systems very appealing as supramolecular hosts for electron-transfer processes.

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“…Since their discovery [1], unique interactions with biomolecules have been expected and also anticipated from the toxological point of view, because fullerenes have recently been synthesized on a large scale and many researchers have been exposed to them, mainly in the electrochemical field. There are a few interesting studies concerning the biological activities of water-soluble [60]fullerene (C60) derivatives such as DNA-cleaving activity [2] and HIV-1 inhibition activity [3,4]. As for unfunctional fullerenes, owing to their low solubility in water, it is hard to examine the biological activities of fullerenes alone especially in in vitro systems.…”

Section: Introductionmentioning

confidence: 99%

Novel harmful effects of [60]fullerene on mouse embryos in vitro and in vivo

et al. 1996

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Abstract[60]Fullerene (C60) was solub'dized with poly(vinylpyrrolidone) (PVP) in water, and the aqueous solution was applied to a mouse midbrain cell differentiation system. On incubation of C60 with various concentrations of PVP, cell differentiation and proliferation were potently inhibited, although weaker than the vehicle controls. C60 was clearly distributed into the yolk sac and embryos by intraperitoneal administration to pregnant mice at 50 mghtg and had a harmful effect on both conceptuses by microscopical evaluation. This in vivo and in vitro action on embryogenesls is a novel and seriously harmful activity of C60.

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Inhibition of the HIV-1 protease by fullerene derivatives: model building studies and experimental verification

Cited by 936 publications

References 0 publications

Phototoxicity and cytotoxicity of fullerol in human lens epithelial cells

Phototoxicity and cytotoxicity of fullerol in human lens epithelial cells

Cyclodextrin-[60]fullerene conjugates: synthesis, characterization, and electrochemical behavior

Novel harmful effects of [60]fullerene on mouse embryos in vitro and in vivo

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