Biological Activity of Water-Soluble Fullerenes. Structural Dependence of DNA Cleavage, Cytotoxicity, and Enzyme Inhibitory Activities Including HIV-Protease Inhibition

Abstract

Two different classes of water-soluble fullerene derivatives, detergent-type and sphere-type, were synthesized. The derivatives were evaluated for their biological activities including cytotoxicity, DNA cleavage, and inhibition of HIV-protease and other enzymes. Both classes of compounds display generally similar behavior except for their cytotoxicity spectra against several cell lines. The fullerene derivatives bearing N-methylpyrrole were found to be photo-inactive with respect to DNA cleaving activity and cytotoxicity. A study on the kinetics for the inhibition of HIV-protease with detergent type derivative revealed that the compound is a potent fullerene-based HIV protease inhibitor, inhibiting the enzyme activity in a reversible and competitive manner with a Ki value of 0.32 μM.

C60 Carboxyfullerene Exerts a Protective Activity against Oxidative Stress-Induced Apoptosis in Human Peripheral Blood Mononuclear Cells

“…This could mean that the lowering of apoptotic rate or the delaying of apoptosis by carboxyfullerene could also be due to other activities of the compound located "downstream" to mitochondria in the apoptotic cascade. In fact, it has been recently demonstrated that the carboxyfullerene derivatives exert a considerable potential as enzyme inhibitors (24) and therefore they could inhibit the protease cascade. Further studies are in progress to identify possible effects of carboxyfullerene derivatives on the caspase cascade.…”

[60]Fullerene Amino Acids and Related Derivatives

“…[60]Fullerene derivatives exhibit a range of interesting biological activities including inhibition of HIV enzymes [4][5][6][7][8][9][10][11][12] , photoinduced cytotoxicity via selective cleavage of DNA [13][14][15][16][17] and as a smooth muscle relaxant [18][19][20] . In addition, other interesting reports of fullerene derivatives of biologically significant molecules such as lipids 21 , saccharides 22 , oligonucleotides [23][24] and amino acids have appeared in the literature.…”

Organofullerene Materials

“…Recently, the synthesis of a functionalized fullerene having a DNA minor groove binder and an oligonucleotide chain covalently linked to the cage via 1,3-dipolar cycloaddition of the appropriate azomethine ylides was reported [282][283][284]. The design of the latter synthesis was based on an already established idea that coupling of fullerenes to a minor groove binder leads to higher affinity and specificity of the derivatives towards target DNA [285]. The construction of fullerene-DNA hybrid materials allows transmission electron microscopy (TEM) imaging of deoxyribonucleic acid without the use of any heavy metal.…”