CARBON-BASED PHARMACEUTICALS AS A NOVEL PROLONGEVITY STRATEGY
E.N. Gorban, V.K. Koltover
Bio-ReliInstitute of Gerontology, National Academy of Medical Sciences, Kiev, Ukraine, and Reliability Group, Institute of Problems of Chemical Physics, RAS, Chernogolovka, Moscow Region, 142,432 Russia
The aim of this study was to demonstrate the prospects of applications
of the novel carbon-based pharmaceuticals, namely - enterosorbents and
fullerenes in biomedical gerontology. We present the results of our own
studies as well as the analytical review of the literature data that
were available up to now. The dietary enterosorbent, SKN non-coated
nitrogen-containing carbon, was found to increase the mean value of
male Wistar rats' life-span by 43%, that is comparable with the
life-span prolongation effects of the calorie-restricted diets (Frolkis
et al., 1989). Some antioxidants, like butylated hydroxytoluene (BHT),
when regularly administered into the diets, were also found to increase
the life-spans of the animals up to 30% (Harman, 1968; Frolkis et al.,
1990). The discovery of new carbon allotropes, the fullerenes (Kroto et
al., 1985), has furthered the searching of novel carbon-based drugs.
Various water-soluble multi-hydroxyl fullerenes (fullerenols), such as
C60(OH)n, demonstrating antioxidant properties have been synthesized
recently. Furthermore, endohedral metallofullerenes (M@C2n) were
synthesized, which are carbon clusters that contain metal atoms (M =
La, Sc, Y, etc.) trapped within a fullerene cage. M@C2n hold much
promise as the contrast agents for NMR imaging. For example, relaxivity
of Gd-fullerenol has turned out to be 20-folds higher than that of
Gd-DTPA (Mikawa et al., 2001). While Gd-DTPA accelerates the NMR
relaxation of water protons owing to its large dipolar magnetic moment
and long electron spin-relaxation time, the 'spin leakage' of the
fullerene shell supplies more effective relaxation mechanism through
the contact coupling of the electron spin of M@C82 with the solvent
nuclear spins (Koltover et al., 2002). Furthermore, M@C2n with the
appropriate particle-emitting radionuclides inside, among them,
beta-emitting 89Sr, 90Y, 47Sc, 64Cu, 149Pr, 153Sm, 166Ho, and 177Lu can
be synthesized, while advances in the molecular biotechnology provide
targeting vectors to deliver therapeutic doses of the ionizing
radiation with high specificity for treatment of metastasis cancer
tumor cells. Thus, M@C2n, due to their unique physical and chemical
properties, provide obvious prospects for designing novel paramagnetic
probes and therapeutic radiopharmaceuticals with solitary biomedical
features.
This research was sponsored by the Russian Foundation for Basic
Research, grant 01-03-32945.
Key words:
aging, life-span prolongation, fullerenes, eneterosorbents
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