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The effect of synthetic nucleoside derivatives on the growth and survival of cultured human ovarian cancer cells (line SKOV-3) and normal human lung fibroblasts has been investigated. The dialdehyde derivatives of uridine, 1-β-D-erythrofuranosyl uracil and 3′-O-β-D-ribofuranosyl-2′-deoxythymidine exhibited a marked toxic effect on SKOV-3 cells, while their unoxidized analogues did not exhibit such action. Cultured human fibroblasts were less susceptible to the damaging effect of the dialdehyde nucleosides. The dialdehyde derivative of 1-β-D-erythrofuranosyl uracil demonstrated the highest difference in its cytotoxic effect on these cultures: 50% or higher suppression of SKOV-3 cells growth was achieved at the concentrations of this compound ten times lower than in the case of normal fibroblasts.

Tripeptide Pro-Gly-Pro (PGP) belongs to the group of biologically active regulatory peptides that are resistant to peptidases. This makes it possible to use it as a C-terminal fragment of peptide agents Semax and Selank. In recent years, the independent effects of PGP were revealed. The question was raised of whether PGP contributes to the action of pharmaceutical agents that contain this peptide as a fragment. Genome-wide analysis was performed to examine the PGP impacts on the transcriptome of rat cerebral cortex in experimental ischemia. We compared the gene expression levels in animals exposed to ischemia and PGP and in rats of the ischemia control group in 3 and 24 h after the permanent occlusion of the left middle cerebral artery. The altered expression of 29 genes was detected in 3 h, while the altered expression of 57 genes was detected in 24 h. The proteins encoded by these genes fulfill various functions, such as cytokines, transport proteins, transcription factors, transmembrane receptors, etc. Biological processes associated with the genes with altered expression under experimental conditions were determined. It was shown that PGP affects a number of processes involved in the functioning of various body systems. The expression of genes associated with the immune response process changed most significantly a day after the occlusion of the middle cerebral artery. The predominant effect of the suppression of the expression of the immune system genes was observed.

Neurotrophins regulate key functions of nervous tissue cells. Analysis of neurotrophin mRNA expression is an appropriate tool to assess therapeutic efficiency of antistroke drugs. We have analyzed the effect of synthetic peptide semax and its C-terminal Pro-Gly-Pro tripeptide on mRNA expression of neurotrophins Ngf, Bdnf, and Nt-3 and their receptors TrkA, TrkB, TrkC, and p75 in rat frontal cortex, hippocampus, and cerebellum after bilateral common carotid artery occlusion. The animals were decapitated at 30 min and 1, 2, 4, 8, 12, and 24 h after the operation. The mRNA expression of neurotrophins and their receptors was assessed by relative quantification using real-time RT-PCR. Our results demonstrated that ischemia caused a significant decrease in gene expression in the hippocampus. Semax and PGP treatment affected the expression of neurotrophins and their receptors predominantly in the frontal cortex and hippocampus of the ischemized animals. In the frontal cortex, Semax treatment resulted in a decrease of mRNA level of neurotrophin receptors, while PGP treatment increased the level of these mRNA. Maximal neuroprotective effect of both peptides was observed in the hippocampus 12 h after occlusion. A decrease of gene expression of neurotrophins and their receptors caused by the occlusion was overcome by Semax and PGP. These results clarify the mechanism of Semax action and reveal certain features of mRNA expression of neurotrophins and their receptors under experimental conditions.