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Information × Registration Number 0220U104771, 0120U103077 , R & D reports Title Interrelations between immunomodulatory and antitumor actions of new heterocyclic compounds (thiazole and 4-thiazolidinone derivatives) popup.stage_title Head Lootsik Maxim D., Доктор біологічних наук Registration Date 27-12-2020 Organization Institute of Cell Biology popup.description2  Twelve newly synthesized 4-thiazolidinone derivatives were studied towards tumor and pseudo-normal mammalian cell in vitro. Compounds Les-6287, Les-6294 and Les-6009 demonstrated high toxic effect towards tumor cells. Compounds Les-6287 and Les-6294 had a more pronounced cytostatic activity towards Jurkat T-leukemia cells (cytotoxicity index IC50 was 1.3 and 3.4 μM, respectively). The substance Les-6009 was highly toxic towards tumor cells of MCF-7, HCT116, HepG2 lines (IC50 was in the range of 0.7-11.4 μM). All 4-thiazolidinone derivatives studied demonstrated low toxicity towards pseudo-normal NaCaT human keratinocytes (IC50 was 73.6 μM and more), Les-6009 - towards Balb3T3 mice fibroblasts (IC50 = 24.0 μM). The tested substances did not intercalate into a DNA molecule and did not bind with plasmid DNA. According to the DNA comet analysis, the Les-6287, Les-6294 and Les-6295 caused the formation of single-strand breaks in the DNA of Jurkat T human leukemia cells. The Les-6009 caused significant DNA damage in HepG2 human hepatocarcinoma cells and minor DNA damage in Balb3T3 mice fibroblasts. Western blot analysis showed that Les-6287, Les-6294 and Les-6295 increased the amount of cleaved caspase 3 and the cleaved PARP1, the DNA repair enzyme, as well as increased the amount of proapoptotic protein Bax, and decreased the number of antiapoptotic protein Bcl-2 in Jurkat cells. Compound Les-6009 caused activation of caspase 3, cleavage of the PARP1 and an increase in the amount of Bax protein in HepG2 cells. Les-6009 did not affect the passage of cells through the G1/S phase of the cell cycle. Product Description popup.authors Antonyuk Volodymyr O. Barska Maryna L. Klyuchivska Olga Yu. Lootsik Maxim D. Starykovych Marina O. Stoika Rostyslav S. Finiuk Nataliya S. popup.nrat_date 2020-12-26 Close