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Here, we report the identification and functional characterization of the Streptomyces globisporus 1912 gene lndYR, which encodes a GntR-like regulator of the YtrA subfamily. Disruption of lndYR arrested sporulation and antibiotic production in S. globisporus. The results of in vivo and in vitro studies revealed that the ABC transporter genes lndW–lndW2 are targets of LndYR repressive action. In Streptomyces coelicolor M145, lndYR overexpression caused a significant increase in the amount of extracellular actinorhodin. We suggest that lndYR controls the transcription of transport system genes in response to an as-yet-unidentified signal. Features that distinguish lndYR-based regulation from other known regulators are discussed.

10 and 50 µM activate superoxide dismutase and lead to a decrease of the activity of catalase and glutathione peroxidase. This effect suggests that the change in the activity of enzymes leads to accumulation of H 2 O 2 in the lymphoma cells. Such results indicate that the studied substance can realize its cytotoxic effect through the action of the antioxidant system. The obtained data can be used to carry out further preclinical studies of the thiazole derivatives as potential antitumor drugs.

Background. A pronounced cytotoxic action of the thiazole derivatives complexed with polymeric carriers on tumor cells in vitro was reported earlier, while no cytotoxicity of these compounds was detected toward noncancerous cells. It was found that thiazole derivatives at concentrations of 10 and 50 µM affected lymphoma cell ultrastructure in vitro. The purpose of this work was to investigate the effect of thiazole derivative 8-methyl-2-Me-7-[trifluoromethyl-phenylmethyl]-pyrazolo-[4,3-e]-[1,3]- thiazolo-[3,2-a]-pyrimidin-4(2H)-one (PP2) and its complexes with polymeric carriers poly(VEP-co-GMA)-graft-mPEG (Th12) and poly(PEGMA) (Th14) on the ultrastructure of lymphoma cells in vivo. Materials and Methods. Experiments were conducted on white wild-type male mice with grafted NK/Ly lymphoma. Ascite tumors were created by intreperitoneal inocu­lation of 1–2 mln of Nemet–Kelner lymphoma cells to mice. On the 12th day after inoculation, the body weight of animals was increased by 140–160 % mostly due to ascites growth. For treatment of ascites three solutions of the chemical compounds were prepared: PP2, PP2 + Th12, PP2 + Th14 and administered to the mice intraperitoneally for 5 days. The final concentration of PP2 was 5 mg/kg of body weight. Abdominal drainage from ascites was performed with a sterile syringe under chloroform anesthesia on the 10th day after the start of treatment. The ultrastructure of the cells was examined by electron microscopy. Results. Еlectron microscopy study showed that control lymphoma cells have a special subcellular formations such as a relatively large nucleus, and specific plasma membrane filaments. The effects of thiazole derivative revealed apoptotic and necrotic manifestations of cytotoxicity, such as a deformation and disintegration of nucleus, a decreased nucleus/cytoplasm ratio, a destruction of the plasma membrane and a change of mitochondria shape. The studied compound complexed with polymeric carriers caused an apoptotic-like changes in lymphoma cells. Under the action of such complexes, the nucleus/cytoplasm ratio decreased and the area of mitochondria increased. Conclusions. The obtained results suggest that the tested compounds induce apoptosis in tumor cells. Complexes of thiazole derivative with polymers do not impair the effect of the compound on lymphoma cells. The obtained data can be used to carry out further preclinical studies of thiazole derivatives complexed with polymeric carriers as potential antitumor drugs.

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