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Vimal K. Jain, Volume 1 Issue 1 April 2013
The compounds containing COOH groups are associated in the solid state through hydrogen bonding."
Having isolatedand characterized several organoselenium compounds, we have evaluated their free radical scavenging ability and GPX mimicking and antioxidant activities both in-vitro and in-vivo. 9-13 A few case studies are presented here. Reactions of organoselenium compounds with HO* radicals and one electron oxidants (Cl, Br,"), generated by pulse radiolysis techniques, have been studied by absorption spectroscopy. The diselenides after the reaction with HO radicals generate diselenide radical cation with concomitant formation of H2O or HO from HO* radicals. The diselenides react with HO radicals11 with rate constants of ~1010M-1 s-1.
Since these compounds showed free radical scavenging properties, their potential as an antioxidant and mimics of GPX has been evaluated by several in-vitro and in-vivo experiments and a few are briefly mentioned here. Red blood cell (RBC) membranes are rich in polyunsaturated fatty acids (lipids) which are susceptible to free radicals mediated peroxidation (lipid peroxidation). As a consequence the RBC membrane undergoes quick damage and loses its integrity which results in to release of hemoglobin (hemolysis) and intracellular potassium ions. When organoselenium compounds, showing peroxyl radical scavenging activity, are present in RBC, both hemolysis and potassium ions release are inhibited.12 We observed that diselenides are more efficient than corresponding monoselenides in reducing the existence of radicals.
Several in-vivo experiments have been carried out on Swiss Albino mice. Their survival against sub- and supralethal doses of-radiation in the presence and absence of organoselenium compounds has been evaluated. It has been observed that there was 35% higher survival of mice administered with organoselenium compounds when whole body was exposed to y-rays (dose rate 0.52 Gy/min). Several tissues, such as hepatic, spleen and gastrointestinal tract, are also highly sensitive to radiation. Thus radio-protective efficacy of organoselenium compounds was also evaluated by assessing protection of some of these tissues.13 The effect of diselenopropionic acid on gastrointestinal tissue was evaluated. The histopathology results revealed that there is a significant protection of the tissue when administered with the diselenopropionic acid before exposure to-radiation.
Conclusion: We have designed and synthesized several organoselenium compounds and characterized them by various techniques. Most of these compounds show
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free radical scavenging activity, among them 3,3'diselnodipropionic acid and nicotinamide based selenium compounds are highly potent. Selenoxide can be reaction intermediate in scavenging ROS. These compounds have potential as radio-protectors.
References
1. L. Flohé, W. A. Günzler and H. H. Schock, FEBS Lett., 32 (1973) 132.
2. J. T. Rotruck, A. L. Pope, H. E. Ganther, A. B. Swanson, D. G. Hafeman and W. G. Hoekstra, Science, 179 (1973) 588.
3. G. Mugesh, W. W. duMont and H. Sies, Chem. Rev., 101 (2001) 2125.
4. A. J. Mukherjee, S. S. Zade, H. B. Singh and R. B. Sunoj, Chem. Rev., 110 (2010) 4357.
5. S. Dey, N. Ghavale, A. Hodge, V. K. Jain, G. Kedarnath, L. B. Kumbhare, P. P. Phadnis, P. Prabhu, A. Wadawale and K. I. Priyadarsini, Preparation of organoselenium compounds, BARC/2009/1/003.
6. A. S. Hodage, P. P. Phadnis, A. Wadawale, K. I. Priyadarsini and V. K. Jain, Org. & Biomolecular Chem., 9 (2011) 2992.
7. C. P. Prabhu, P. P. Phadnis, A. P. Wadawale, K. I. Priyadarsini, and V. K. Jain, unpublished results.
8. A. S. Hodage, P. P. Phadnis, A. Wadawale, K. I. Priyadarsini, and V. K. Jain, X-ray Structure Analysis Online, 25 (2009) 101.
9. V. K. Jain and K. I. priyadarsini, Proc. Nat. Acd. Sci., 80 (2010) 269.
10. A. Kunwar, B. Mishra, A. Barik, L. B. Kumbhare, R. Pandey, V. K. Jain and K. I. Priyadarsini, Chem. Res. Toxicology, 20 (2007) 1482.
11. B. Mishra, L. B. Kumbhare, V. K. Jain and K. I. Priyadarsini, J. Physical Chem. B, 112 (2008) 4441. 12. B. S. Kumar, A. Kunwar, A. Ahmad, L. B. Kumbhare, V. K. Jain and K. I. Priyadarsini, Radiation & Environmental Biophysics, 48 (2009) 379.
13. A. Kumar, P. Bansal, S. J. Kumar, P. P. Bag, P. Paul, N. D. Reddy, L. B. Kumbhare, V. K. Jain, R. C. Chaubay, M. K. Unnikrishnan and K. I. Priyadarsini, Free Radical Biology & Medicine, 48 (2010) 399.
14. O. Skaff, D. I. Pattison, P. E. Morgan, R. Bachana, V. K. Jain, K. I. Priyadarsini and M. J. Davies, Biochem. J., 441 (2012) 305.