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.

Essential metalloelement chelates presents a promising class of compounds for search and development of novel anti-radiation agents, study of which offers a new approach to overcome the pathological effects of ionizing radiation. In this study Cu(II) chelates of Nicotinyl-L-Tyrosinate and Nicotinyl-L-Tryptophanate Schiff Bases were synthesized and investigated as radioprotectors in animal experiments against injuries caused by ionizing irradiation. Based on the assessment of average life-span indices and 30-day animal survival after radiation exposure at LD50/30 (4.8 Gy) or LD100/30 (8.7 Gy) the radioprotective effects of 0 mg/kg (Vehicle), 10 mg/kg, 20 mg/kg, or 40 mg/kg Cu(II)(Nicotinyl-L-Tyrosinate)2 or Cu(II)(Nicotinyl-L-Tryptophanate)2 as well as their parents Schiff Bases were studied in case of single subcutaneous and oral administration to rats 1, 3, 6 and 24 hours prior to X-ray irradiation. The mixture of 4% propylene glycol and 1.4% polyvinyl alcohol in saline was used as a Vehicle for the administration of compounds to animal organism. According to the results obtained, administration of the metallochelates to the rat organism prior to X-ray irradiation provided strong radioprotective effects expressed upon application of all considered dose, mode and time treatment schedules: in groups of animals treated with Cu(II) chelates there was an remarkable increase in the indices of survival and average life-span in a 30-day period post exposure compared to the control Vehicle treated -irradiated rats. The appropriate parents Schiff Bases Nicotinyl-L-Tyrosinate and Nicotinyl-LTryptophanate also exerted the radioprotective action. However, these compounds were active as effective radioprotectors only in case X-ray irradiation at a dose level equal to or less than LD50/30. Data of analyses indicated that Cu(II) chelates as well as their initial amino acid Schiff Bases did not avert the development of disturbances of hematological indices of animals exposed at LD50/30. However, the findings of immunological studies have demonstrated the inhibiting effects of these compounds on circulating immune complexes (CICs) in blood plasma, which are the major mediators of immune response and are considered as indicators of the autoimmune and inflammatory components of radiation-induced upregulated immune response. Unlike to Nicotinyl-L-Aminoacidate Schiff Bases their corresponding Cu(II) chelates diminished the harmful effects of radiation-induced CICs formation not only in case of irradiation at LD50/30, but also at much higher radiation dose levels. Thus, the single administration of Cu(II)(Nicotinyl-LTyrosinate)2 and Cu(II)(Nicotinyl-L-Tryptophanate)2 at non-toxic doses provides effective radiation protection and high level of survival of exposed animals. Research is performed in the frames of ISTC A-1321 Project.

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The synthesis of ethyl esters of 2-salicylidene derivatives of tyrosine, y -amino butyric acid (GABA), and glycyl-glycine was carried out. These Schiff base ligands present themselves as pale-yellow crystals. These Schiff bases have been used to prepare Mn (11) complexes by allowing them to react with Mn (11) ion. Their possible structures were determined using several analytical and physical-chemical techniques. These Mn (11) complexes are obtained as gray crystals. Cytogenetic studies of bone marrow cells from whole-body 4.2 Gy (0.42 Gy/min dose rate) irradiated white inbred rats revealed that prior administration of 10mgkg of the Mn chelate of the ethyl ester of the 2salicylidene derivative of tyrosine was radioprotective. Compared to two control groups: (I)animals exposed to irradiation only and (Ii) -animals treated with vehicle before irradiation, there was a 7-fold decrease in number of chromosome aberrations. Mn-chelates of 2-salicylidene GABA and glycylglycine were less radioprotective. The studies compounds have just as superoxide scavanging activity. Introduction:Many works have established that essential transition metal complexes of amino acids and peptides (1-7) and 2-salicylidene amino-acid Schiff bases (8,9) with anti-tumour, antioxidant, and superoxide dismutase-mimetic activities have radiation protective and radiation recovery activities. However, these publications have been concerned mainly with complexes of Cu (11), Zn (11), Co (II), Ni (II), Fe (Ii), and Fe (111) formed with either amino acids or their Schiff bases. Scientific publications and data for Mn (11) amino acids and peptides complexes (10-12) and Schiff basis of amino acids are scanty (13). There were two reasons to perform the research presented: