Schiff bases and their metal-complexes are versatile compounds exhibiting a broad range of biological activities and thus actively used in the drug development process. The aim of the present study was the synthesis and characterization of new Schiff bases and their copper (II) complexes, derived from L-tryptophan and isomeric (2-; 3-; 4-) pyridinecarboxaldehydes, as well as the assessment of their toxicity in vitro. The optimal conditions of the Schiff base synthesis resulting in up to 75-85% yield of target products were identified. The structure-activity relationship analysis indicated that the location of the carboxaldehyde group at 2-, 3- or 4-position with regard to nitrogen of the pyridine ring in aldehyde component of the L-tryptophan derivative Schiff bases and corresponding copper complexes essentially change the biological activity of the compounds. The carboxaldehyde group at 2- and 4-positions leads to the higher cytotoxic activity, than that of at 3-position, and the presence of the copper in the complexes increases the cytotoxicity. Based on toxicity classification data, the compounds with non-toxic profile were identified, which can be used as new entities in the drug development process using Schiff base scaffold.

During our previous research, we isolated lactobacilli strains: E5-1, M1-3 and ZPZ, that have antagonistic activities against A. baumannii, S. aureus, K. pneumoniae and Enterobacter gergoviae that are prevalent in Yerevan hospitals. The aim of the current investigation was to evaluate radioprotective activities of these strains. 90 healthy adult Wistar rats in the weight range 150-200g were randomly placed into the following nine groups: control, control-placebo, irradiated, three control-lactobacilli and three irradiatedlactobacilli. The three irradiated-lactobacilli groups received an appropriate feeding cannula for seven days prior to receiving a 4.5 Gy irradiation. A significant decrease in the blood leukocyte count (WBC) was described after the seventh day of rats' irradiation ((0.8050.07)x10 9 /L vs. (7.1250.39) x10 9 /L and (6.8450.77)x10 9 /L; P<0.05). We did not find any significant changes in the rats' blood glucose levels (BGL) adopted placebo ((5.7950.37) mMol/L vs. (6.4250.33) mMol/L; P>0.05), but an insignificant increase within the normal range was observed for the irradiated-E5-1 rats ((5.7950.37) mMol/L and ((6.4350.33) mMol/L vs. (8.1250.2) mMol/L; P < 0.05)). Parallel to this, we described a statistically confirmed decrease of WBC after the trial by the LactobacillusM1-3 ((5.2150.12)x10 9 /L vs. (7.1250.39)x10 9 /L and (6.8450.77)x10 9 /L; P<0.05). Also, the irradiated-E5-1 rats kept their initial BGL after the irradiation: (7.7050.16) vs. 6.74; P<0.05 (in comparison with irradiated rats) and (7.750.16) vs. (8.1250.2); P>0.05 (in comparison with control-E5-1 rats). This group of rats were also characterized by the statistically confirmed increase of WBC in comparison with its irradiated controls ((0.8050.07)x10 9 /L vs. 1.58x10 9 /L; P<0.05), and decrease of WBC in comparison with its controls ((6.750.38)x10 9 /L vs. 1.58x10 9 /L; P<0.05). These findings are of significance for the LactobacillusE5-1 application as a starter for the production of functional food with radioprotective activities.

The new synthesized Cu(II) chelates of amino acids Schiff bases were studied as a potential radioprotectors. Male albino rats of Wistar strain were exposed to X-ray whole-body irradiation at 4.8 Gy. This dose caused 30% mortality of the animals (LD30). The survival of animals exposed to radiation after preliminary administration of 10 mg/kg Cu(II)(Nicotinyl-L-Tyrosinate)2 or Cu(II)(Nicotinyl-L-Tryptophanate)2 prior to irradiation was registered about 80 and 100% correspondingly. Using spectrophotometric melting and agarose gel electrophoresis methods, the differences between the DNA isolated from irradiated rats and rats pretreated with Cu(II) chelates were studied. The fragments of DNA with different breaks were revealed in DNA samples isolated from irradiated animals. While, the repair of the DNA structure was observed for animals pretreated with the Cu(II) chelates. The results suggested that pretreatment of the irradiated rats with Cu(II)(Nicotinyl-L-Tyrosinate)2 and Cu(II)(Nicotinyl-L-Tryptophanate)2 compounds improves the liver DNA characteristics.

This research was performed to determine whether or not treatment of burn-injured rats with Cu(II)2(3,5-diisopropylsalicylate)4(Cu(II)2(3,5-DIPS)4) facilitated recovery from burn-injury. Four groups of adult male rats received a standard skin burn 1 h before an initial subcutaneous treatment which was continued daily for three days with either 0, 5, 10 or 20micromol Cu(II)2(3,5-DIPS)4/kg body mass. A fifth group was given no treatment. A sixth group served as a non-burn-injured non-treated normal control group. At 3 h and on days 1, 2, 3, 7 and 14 post-burn-injury blood samples were obtained from rats in all groups for the determination of leukocyte, platelet and erythrocyte counts, clotting times, hemoglobin and hematocrit values. Total protein and middle mass peptides in plasma, as well as plasma lipid and erythrocyte membrane peroxidation products were determined on days 7 and 14. Burn wound healing and body mass were determined daily from day 0 to 6 with a notation of crust rejection by day 14. Treatment with Cu(II)2(3,5-DIPS)4 produced effects consistent with a facilitation of Cu-dependent immune-mediated physiological inflammatory responses to burn injury. It is concluded that treatment of burn injury with Cu(II)2(3,5-DIPS)4 supports Cu-dependent physiological responses involved in overcoming burn injury, which may have been further optimized by continued treatment beyond day 2, the last day of treatment.