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Information × Registration Number 0216U006329, 0116U005365 , R & D reports Title Search for new potential anticancer agents among heterocyclic derivatives containing thiazolidinone fragment in the molecule popup.stage_title Head Zelisko Nataliya Ivanivna, Registration Date 08-12-2016 Organization Danylo Halytsky Lviv National Medical University popup.description2 Aim of research -synthesis of heterocyclic derivatives containing thiazolidinone fragment in the molecule and search among them active and low-toxic compounds as potential anticancer agents. Objects of research - thiopyrano [2,3-d] thiazole derivatives, the reactions of [2 + 4] - cyclocondensation, heterocyclization, thionation, acylation- hetero-Diels-Alder reactions, tandem reactions. Methods: organic synthesis, NMR spectroscopy, chromatography-mass spectrometry, X-ray analysis, elemental analysis, MTT test, pharmacological screening in vitro. It is shown that [4 + 2] - cyclocondensations and tandem acylation - hetero-Diels-Alder reactions are effective approaches for the synthesis of thiopyrano [2,3-d] thiazoles, which allowed to obtain a series of new compounds, determine their structure, learn physico-chemical parameters and antitumor activity. 5-Arylidene-4-thioxo-2- thiazolidinones with trans-aconitic acid in hetero-Diels-Alder reactions pass with spontaneous decarboxylation, which allowed to obtain a series of rel- (6R, 7R) -7-aryl-6- carboxymethylene -2- oxo-3,5,6,7-tetrahydro-2H- thiopyrano [2,3-d] [1,3] thiazole-6-carboxylic acids and chromeno[4',3':4,5]thiopyrano[2,3-d]thiazoles. Mentioned derivatives were also synthesized via an alternative approach. It was shown that polycyclic 2-(2,6-dioxo-3,5a,6,11b-tetrahydro-2H,5H-chromeno[4',3':4,5]thiopyrano[2,3-d]thiazole-5-yl)-acetic acid is new reagent for the structurally complex heterocycles with chromene ring opening. In the study of antitumor activity in vitro it is found that compound 5 has the most severe toxicity on tumor cell leukemic origin: average index substances cytotoxicity IC50 = 33.5 µM. Compounds 26 (IC50 = 1.3 µM) and 9d (IC50 = 3.9 µM) have the most severe toxicity on tumor cell leukemic origin. Compound 9d is also a promising agent for the treatment of malignant gliomas. Compounds 26 and 9d cause induction of apoptosis, which is mediated by irreversible changes of mitochondria and endoplasmic reticulum of the cell. Also it is found that compounds 26 and 9d inhibit cell division in the G1 phase of the cell cycle. Product Description popup.authors Грабовий Петро Васильович Зеліско Наталія Іванівна Фінюк Наталія Степанівна popup.nrat_date 2020-04-02 Close