Cyclic Amino Acid Derivatives as New Generation of Radioprotectors

Abstract

Recently we synthesized a number of Schiff-base cyclic amino acid derivatives, and their metallic complexes as radioprotectors. Our preliminary investigations revealed four compounds, viz., nicotinyl-L-tryptophan, nicotinyl-L-tyrosine, and copper complexes of nicotinyl-L-tryptophan and picolinyl-L-tryptophan, possessing free radical neutralization capabilities. In the present investigation, we studied the effects of the selected compounds on survival rate, immune and antioxidant systems of the organism in the conditions of IR using animal model of irradiation injury. As the indicators of the immune system state we considered major mediators of the immune response, the complement system and the immune complexes. As the indicators of the antioxidant system functional state, we considered enzymes catalyzing free radical neutralization reactions, CuZn-superoxide dismutase and catalase. The results indicate that nicotinyl-L-tryptophan, nicotinyl-L-tyrosine and copper complex of picolinyl-L-tryptophan increase survival rate and possess immune-modulating and antioxidant system capacity elevating effects in the conditions of IR. These compounds stabilize and reactivate defense biomolecules, regulate the immune response, and increase radio-sensitivity threshold, and hence may be considered as a new generation of highly efficient multifunctional radioprotectors targeting native defense systems of the organism.