Development of Novel Pyridine-Thiazole Hybrid Molecules as Potential Anticancer Agents.

Autor: Ivasechko I; Institute of Cell Biology of National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, Ukraine., Yushyn I; Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, Ukraine., Roszczenko P; Department of Biotechnology, Faculty of Pharmacy, Medical University of Bialystok, 15-089 Bialystok, Poland., Senkiv J; Institute of Cell Biology of National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, Ukraine., Finiuk N; Institute of Cell Biology of National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, Ukraine., Lesyk D; Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, Ukraine., Holota S; Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, Ukraine., Czarnomysy R; Department of Synthesis and Technology of Drugs, Faculty of Pharmacy, Medical University of Bialystok, 15-089 Bialystok, Poland., Klyuchivska O; Institute of Cell Biology of National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, Ukraine., Khyluk D; Department of Organic Chemistry, Medical University of Lublin, Aleje Racławickie 1, 20-059 Lublin, Poland., Kashchak N; Institute of Cell Biology of National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, Ukraine., Gzella A; Department of Organic Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland., Bielawski K; Department of Synthesis and Technology of Drugs, Faculty of Pharmacy, Medical University of Bialystok, 15-089 Bialystok, Poland., Bielawska A; Department of Biotechnology, Faculty of Pharmacy, Medical University of Bialystok, 15-089 Bialystok, Poland., Stoika R; Institute of Cell Biology of National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, Ukraine., Lesyk R; Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, Ukraine.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2022 Sep 21; Vol. 27 (19). Date of Electronic Publication: 2022 Sep 21.
DOI: 10.3390/molecules27196219
Abstrakt: Novel pyridine-thiazole hybrid molecules were synthesized and subjected to physico-chemical characterization and screening of their cytotoxic action towards a panel of cell lines derived from different types of tumors (carcinomas of colon, breast, and lung, glioblastoma and leukemia), and normal human keratinocytes, for comparison. High antiproliferative activity of the 3-(2-fluorophenyl)-1-[4-methyl-2-(pyridin-2-ylamino)-thiazol-5-yl]-propenone 3 and 4-(2-{1-(2-fluorophenyl)-3-[4-methyl-2-(pyridin-2-ylamino)-thiazol-5-yl]-3-oxopropylsulfanyl}-acetylamino)-benzoic acid ethyl ester 4 was revealed. The IC50 of the compound 3 in HL-60 cells of the acute human promyelocytic leukemia was 0.57 µM, while in the pseudo-normal human cell lines, the IC50 of this compound was >50 µM, which suggests that the compounds 3 and 4 might be perspective anticancer agents. The detected selectivity of the derivatives 3 and 4 for cancer cell lines inspired us to study the mechanisms of their cytotoxic action. It was shown that preincubation of tumor cells with Fluzaparib (inhibitor of PARP1) reduced the cytotoxic activity of the derivatives 3 and 4 by more than twice. The ability of these compounds to affect DNA nativity and cause changes in nucleus morphology allows for the suggestion that the mechanism of action of the novel pyridine-thiazole derivatives might be related to inducing the genetic instability in tumor cells.
Databáze: MEDLINE
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