S. D. Brinkevich et al. / Bioorg. Med. Chem. Lett. 22 (2012) 2424–2427
2427
10. Sharma, M. K.; Buettner, G. R. Free Radical Biol. Med. 1993, 14, 649.
11. Burkea, M.; Edgea, R.; Landb, E. J.; Truscott, T. G. J. Photochem. Photobiol., B
2001, 60, 1.
12. Jariwalla, R. J.; Harakeh, S. Subcell. Biochem. 1996, 25, 213.
13. Furuya, A.; Uozaki, M.; Yamasaki, H.; Arakawa, T.; Arita, M.; Koyama, A. H. Int. J.
Mol. Med. 2008, 22, 541.
14. Uchide, N.; Toyoda, H. Molecules 2011, 16, 2032.
15. Bsoul, S. A.; Terezhalmy, G. T. J. Contemp. Dent. Pract. 2004, 5, 1.
16. Parkinson, R. W. U.S. Patent 4 424 232, 1984.
17. Cinatl, J.; Cinatl, J.; Weber, B.; Rabenau, H.; Gumbel, H. O.; Chenot, J.-F.; Scholz,
M. Antiviral Res. 1995, 27, 405.
18. Mathew, D.; Nair, C.-K. K.; Jacob, J. A.; Biswas, N.; Mukherjee, T.; Kapoor, S.;
Kagiya, T. V. J. Radiat. Res. 2007, 48, 369.
compounds in aqueous solutions due to reduction of oxygen- and
carbon-centered radicals. The fully substituted AA derivative, II, is
capable of oxidizing
a-hydroxyl-containing carbon-centered radi-
cals; consequently, it suppresses radiation-induced transformations
of hydroxyl-containing organic compounds. Investigation of antiviral
properties of these compounds has shown that AA, its 6-O-palmitate
(PAA) and 2,3-O-dialkylated derivatives (II and IIa) produce no effect
on replication of HSV-1 in human RD cell culture. At the same time,
2-O-glycosylated derivatives of AA (I and Ia) display marked antiviral
properties against HSV-1.
19. Morisaki, K.; Ozaki, S. Chem. Pharm. Bull. 1996, 44, 1647.
20. Compounds necessary for the study (except II and IIa) were commercially available
and were used without additional purification: Twice-distilled water was used to
prepare aqueous solutions. The standard phosphate buffer was used to
We believe that the antiviral activity of compound I may be due
to the presence of the following combination of properties in this
compound:
maintain the solution pH value at
7
0.05. For solutions of organic
phosphates, the pH value was adjusted to 7 0.05 by adding the required
amounts of perchloric acid. After dissolving the additives (C = 10ꢁ3 mol/l), the
solutions were dispensed in ampoules, saturated with argon or oxygen, and the
ampoules were sealed. Irradiation of the samples was performed using a MPX-
(a) 2-O-Glycoside of ascorbic acid (I) is capable of inhibiting
fragmentation and recombination reactions of hydroxyl-contain-
ing carbon-centered radicals, which may ensure protection of
vitally important components of uninfected cells from injuries
caused by ROS.
c
-25 M unit (60Co, dose rate 0.44 0.008 Gy/s, absorbed dose range 0.13–
1.6 kGy). Determination of the major molecular products of radiation-induced
transformations of ethanol and ethylene glycol (acetaldehyde and 2,3-
butanediol) was performed using
a
Shimadzu GC-17AAF/APC gas
chromatograph according to procedures described in [Brinkevich, S. D.;
Samovich, S. N.; Shadyro, O. I. High Energ. Chem. 2011, 45, 532.]. Highly
selective spectrophotometric method [Sir Egerton, A. C.; Everett, A. J.; Minkoff,
G. J.; Rudrakanchana, S.; Salooja, K. C. Anal. Chim. Acta. 1954, 10, 422.] was used
to determine H2O2 in the presence of the test compounds. Inorganic phosphate
in the presence of organic phosphates was determined according to [Lin, T-I.;
Morales, M. F. Anal. Biochem. 1977, 77, 10.]. Concentrations of AA, I and II in
aqueous solutions were measured using Specord S600 UV–vis
spectrophotometer. Radiation-chemical yields (G, mol/J) were calculated
from linear portions of plots of the product concentrations (or starting
compounds) versus dose absorbed.
(b) However, unlike AA and its 2,3-disubstituted analog (II), I
does not influence the processes involving oxygen-centered radi-
cals, and hence it does not interfere with realization of physiolog-
ical response of the organism to a viral infection.
The experimental facts and relationships revealed in this study
may be used to perform targeted search for new antiviral agents
among the compounds capable of regulating free radical processes.
21. Boreko, E. I.; Pavlova, N. I.; Zaitzeva, G. V.; Michailopulo, I. A. Vopr. Virusol. (In
Rusian) 2001, 46, 40.
Acknowledgment
22. Baltina, L. A.; Flekhter, O. B.; Nigmatullina, L. R.; Boreko, E. I.; Pavlova, N. I.;
Nikolaeva, S. N.; Savinova, O. V.; Tolstikov, G. A. Bioorg. Med. Chem. Lett. 2003,
13, 3549.
The study was performed under support from the International
Science and Technology Center (ISTC), Grant B-1746.
23. Rotman, D. Med. Hypotheses. 1978, 4, 40.
24. Freeman, G. R. Radiation Chemistry of Ethanol; Washington: NBS, 1974.
25. Brinkevich, S. D.; Shadyro, O. I. High Energ. Chem. 2011, 45, 93.
26. Shadyro, O. I. In Free Radicals in Biology and Environment; Minisci, F., Ed.;
Kluwer Academic Publishers: The Netherlands, 1997; pp 317–329.
27. Edimecheva, I. P.; Kisel, R. M.; Shadyro, O. I.; Kazem, K.; Murase, H.; Kagiya, T. J.
Radiat. Res. 2005, 46, 319.
28. Eklund, H.; Uhlin, U.; Farnegardh, M.; Logan, D. T.; Nordlund, P. Prog. Biophys.
Mol. Biol. 2001, 77, 177.
29. Muller, S. N.; Batra, R.; Senn, M.; Giese, B.; Kisel, M.; Shadyro, O. J. Am. Chem.
Soc. 1997, 119, 2795.
30. von Sonntag, C.; Shuchmann, H.-P. In Radiation Chemistry: Present Status and
Future Trends; Jonah, C. D., Rao, B. S. M., Eds.; Elsevier: Amsterdam, 2001; pp
481–511.
31. Shadyro, O. I.; Yurkova, I.; Kisel, M.; Brede, O.; Arnhold, J. Free Radical Biol. Med.
2004, 36, 1612.
References and notes
1. De Clercq, E. Annu. Rev. Pharmacol. Toxicol. 2011, 51, 1.
2. Schwarz, K. B. Free Radical Biol. Med. 1996, 21, 641.
3. Kaul, P.; Biagioli, M. C.; Singh, I.; Turner, R. B. J. Infect. Dis. 1885, 2000, 181.
4. Repetto, M.; Reides, C.; Carretero, M. L. G.; Costa, M.; Griemberg, G.; Llesuy, S.
Clin. Chim. Acta 1996, 255, 107.
5. Suzuki, S.; Kimura, T.; Ikuta, K. Nippon Rinsho 1998, 56, 75.
6. Akaike, T.; Noguchi, Y.; Ijiri, S.; Setoguchi, K.; Suga, M.; Zheng, Y. M.;
Dietzschold, B.; Maeda, H. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 2448.
7. Larrea, E.; Beloqui, O.; Munoz-Navas, M. A.; Civeira, M. P.; Prieto, J. Free Radical
Biol. Med. 1998, 24, 1235.
8. Akaike, T. Rev. Med. Virol. 2001, 11, 87.
9. Davies, M. B.; Partridge, D. A.; Austin, J. A. Vitamin C: Its Chemistry and
Biochemistry; Royal Society of Chemistry: Cambridge, 1991.
32. Yurkova, I.; Kisel, M.; Arnhold, J.; Shadyro, O. I. Chem. Phys. Lipids 2005, 137, 29.