In the present study we have synthesized a novel amphiphilic porphyrin and its Ag(II) complex through modification of water-soluble porphyrinic structure in order to increase its lipophilicity and in turn pharmacological potency. New cationic non-symmetrical meso-substituted porphyrins were characterized by UV–visible, electrospray ionization mass spectrometry (ESI-MS), 1H NMR techniques, lipophilicity (thin-layer chromatographic retention factor, Rf), and elemental analysis. The key toxicological profile (i.e. cytotoxicity and cell line-(cancer type-) specificity; genotoxicity; cell cycle effects) of amphiphilic Ag porphyrin was studied in human normal and cancer cell lines of various tissue origins and compared with its water-soluble analog. Structural modification of the molecule from water-soluble to amphiphilic resulted in a certain increase in the cytotoxicity and a decrease in cell line-specificity. Importantly, Ag(II) porphyrin showed less toxicity to normal cells and greater toxicity to their cancerous counterparts as compared to cisplatin. The amphiphilic complex was also not genotoxic and demonstrated a slight cytostatic effect via the cell cycle delay due to the prolongation of S-phase. As expected, the performed structural modification affected also the photocytotoxic activity of metal-free amphiphilic porphyrin. The ligand tested on cancer cell line revealed a dramatic (more than 70-fold) amplification of its phototoxic activity as compared to its water-soluble tetracationic metal-free analog. The compound combines low dark cytotoxicity with 5 fold stronger phototoxicity relative to Chlorin e6 and could be considered as a potential photosensitizer for further development in photodynamic therapy.

This study highlights the upregulation of SLC7A5, SLC7A8 and TDO2 in BCC compared with nontumour skin. Our findings imply that amino acid transporters may be further explored as potential targets for future medical treatment.

A new proline-rich polypeptide (PRP-1) has been earlier shown to possess a broad spectrum of biological activities and seems to be a potential medicine. The potential genotoxic properties of PRP-1 and protective effect of PRP-1 against genotoxic action of Mitomycin C (MMC) were analyzed in details in the present work. DNA and chromosome damages were studied in KCL-22 cell line of human myeloid leukemia by the Comet assay and micronucleus induction test, respectively. The results suggest that DNA damages are, at least partly, transient and reparable. PRP-1 at the doses 0.5-2.0 microg/ml does not possess genotoxic activity. Moreover, this peptide expresses both preventive and therapeutic effects against MMC-induced DNA damage. Pre-treatment of cells with PRP-1 also prevents the appearance of daughter cells bearing as heavy MMC-induced DNA/chromosome damages as MNs. Thus, the polypeptide studied is able to protect the cells from genotoxic action of MMC. This defense includes not only DNA but also heritable chromosome damage in post-mitotic cells. Possible mechanisms of PRP-1 protective action are discussed.

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Porphyrins and porphyrin derivatives have an outstanding potential for discovery of novel pharmacological agents due to their ability for numerous chemical modifications and a variety of mechanisms of biological effects. New water-soluble Ag and Zn derivatives of tetrachloride meso-tetra (4-N-oxiethylpyridyl) porphyne were synthesized. Cyto- and genotoxicity of these substances were tested in vitro by the vital dye (trypan blue) exclusion and the micronucleus tests, respectively. Both metalloporphyrins were shown to be cytotoxic for Cos-7 (fibroblast-like African green monkey kidney cells transformed by simian virus 40 [SV40]), DU 145 (epithelial-like cells of human prostate carcinoma), and K-562 (human chronic myeloid leukemia cells) cell lines. At the same time they did not cause chromosome fragmentation in K-562 cell line at as high concentrations as IC(50) (20 micromol/L for Ag and 70 micromol/L for Zn derivative). Thus, the metalloporphyrins tested meet at least two important demands to potential anticancer drugs as they combine the cytotoxicity with low genotoxicity. The three in vitro tumor models used are relevant to further in vitro and in vivo preclinical investigation of the studied metalloporphyrins as potential chemotherapeutics.

A new proline-rich polypeptide (PRP-1) has been earlier shown to possess a broad spectrum of biological activities and seems to be a potential medicine. The potential genotoxic properties of PRP-1 and protective effect of PRP-1 against genotoxic action of Mitomycin C (MMC) were analyzed in details in the present work. DNA and chromosome damages were studied in KCL-22 cell line of human myeloid leukemia by the Comet assay and micronucleus induction test, respectively. The results suggest that DNA damages are, at least partly, transient and reparable. PRP-1 at the doses 0.5-2.0 l g/ml does not possess genotoxic activity. Moreover, this peptide expresses both preventive and therapeutic effects against MMCinduced DNA damage. Pre-treatment of cells with PRP-1 also prevents the appearance of daughter cells bearing as heavy MMC-induced DNA/chromosome damages as MNs.

According to investigations conducted in conditions of irrigated brown meadow soils of the community Vedi in the Ararat region, the application of barda with the dose of 1400 m3 /ha promotes the crops growth and development. Due to its valuable macro-nutrients (N, P, K) the soil’s physicochemical, chemical properties and nutritional regime improves, as well as the crop’s yield capacity increases. In the result of fertilizing the experimental plots with barda, the yield capacity of watermelon has increased by 28.8 % and the grain yield of winter wheat – by 24 %.