Medicinal applications of fullerenes

Abstract

Fullerenes have attracted considerable attention in different fields of science since their discovery in 1985. Investigations of physical, chemical and biological properties of fullerenes have yielded promising information. It is inferred that size, hydrophobicity, three-dimensionality and electronic configurations make them an appealing subject in medicinal chemistry. Their unique carbon cage structure coupled with immense scope for derivatization make them a potential therapeutic agent. The study of biological applications has attracted increasing attention despite the low solubility of carbon spheres in physiological media. The fullerene family, and especially C60, has appealing photo, electrochemical and physical properties, which can be exploited in various medical fields. Fullerene is able to fit inside the hydrophobic cavity of HIV proteases, inhibiting the access of substrates to the catalytic site of enzyme. It can be used as radical scavenger and antioxidant. At the same time, if exposed to light, fullerene can produce singlet oxygen in high quantum yields. This action, together with direct electron transfer from excited state of fullerene and DNA bases, can be used to cleave DNA. In addition, fullerenes have been used as a carrier for gene and drug delivery systems. Also they are used for serum protein profiling as MELDI material for biomarker discovery. In this review we report the aspects of medicinal applications of fullerenes.

Figure 1

Structures of compounds 1 and 2. Copyright © 1998. Reproduced with permission from Brettreich M, Hirsch A. 1998. A highly water-soluble dendro[60]fullerene. Tetrahedron Lett, 39:2731–34.

Figure 2

Structures of Fulleropyrrolidines. Copyright © 2005. Reproduced with permission from Marchesan S, Da Ros T, Spalluto G, et al. 2005. Anti-HIV properties of cationic fullerene derivatives. Bioorg Med Chem Lett, 15:3615–18.

Figure 3

Kinetics of the photodynamic inactivation of SFV by C60. SFV was illuminated with visible light in the presence of C60 under constant stirring and O₂ bubbling (•). Mean values and standard errors from three independent experiments are shown. Controls include the incubation of SFV with C60 without illumination (▽), the illumination of SFV without C60 (○) and the illumination with C60 under constant stirring and flushing with argon ( ) Copyright © 1995. Reproduced with permission from Rywkin S, Ben-Hur E, Reid ME, et al. 1995. Selective protection against IgG binding to red cells treated with phthalocyanines and red light for virus inactivation. Transfusion, 35:414–20.

Figure 4

Closer view of the (HIV PR)-2a complex, showing the H-bond between NH₂ or NH³⁺ groups with Asp 25 and 125. Copyright © 2000. Reproduced with permission from Marcorin GL, Da Ros T, Castellano S, et al. 2000. Design and synthesis of novel [60]Fullerene derivatives as potential HIV aspartic protease inhibitors. Org Lett, 2:3955–8.

Figure 5

Influence of fullerene derivatization on the MELDI protein profile pattern in the m/z range of 2300–6300 (A, B and C) and 10200-20000 (D, E and F); (A and D) dioctadecyl methano[C60]fullerene, (B and E) [C60]fullerenoacetic acid, (C and F) Cu(II)-IDA-[C60]fullerene. Conditions: each spectrum: addition of 350 shots, matrix: SA. Sample: diluted human serum.