Development of Novel Pyridine-Thiazole Hybrid Molecules as Potential Anticancer Agents
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 hum...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/19/6219 |
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| author | Iryna Ivasechko Ihor Yushyn Piotr Roszczenko Julia Senkiv Nataliya Finiuk Danylo Lesyk Serhii Holota Robert Czarnomysy Olga Klyuchivska Dmytro Khyluk Nataliya Kashchak Andrzej Gzella Krzysztof Bielawski Anna Bielawska Rostyslav Stoika Roman Lesyk |
| author_facet | Iryna Ivasechko Ihor Yushyn Piotr Roszczenko Julia Senkiv Nataliya Finiuk Danylo Lesyk Serhii Holota Robert Czarnomysy Olga Klyuchivska Dmytro Khyluk Nataliya Kashchak Andrzej Gzella Krzysztof Bielawski Anna Bielawska Rostyslav Stoika Roman Lesyk |
| author_sort | Iryna Ivasechko |
| collection | DOAJ |
| description | 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 <b>3</b> and 4-(2-{1-(2-fluorophenyl)-3-[4-methyl-2-(pyridin-2-ylamino)-thiazol-5-yl]-3-oxopropylsulfanyl}-acetylamino)-benzoic acid ethyl ester <b>4</b> was revealed. The IC<sub>50</sub> of the compound <b>3</b> in HL-60 cells of the acute human promyelocytic leukemia was 0.57 µM, while in the pseudo-normal human cell lines, the IC<sub>50</sub> of this compound was >50 µM, which suggests that the compounds <b>3</b> and <b>4</b> might be perspective anticancer agents. The detected selectivity of the derivatives <b>3</b> and <b>4</b> 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 <b>3</b> and <b>4</b> 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. |
| first_indexed | 2024-03-09T21:26:53Z |
| format | Article |
| id | doaj.art-b7c986c8e0ab406bb5299519122d24d4 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T21:26:53Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b7c986c8e0ab406bb5299519122d24d42023-11-23T21:07:43ZengMDPI AGMolecules1420-30492022-09-012719621910.3390/molecules27196219Development of Novel Pyridine-Thiazole Hybrid Molecules as Potential Anticancer AgentsIryna Ivasechko0Ihor Yushyn1Piotr Roszczenko2Julia Senkiv3Nataliya Finiuk4Danylo Lesyk5Serhii Holota6Robert Czarnomysy7Olga Klyuchivska8Dmytro Khyluk9Nataliya Kashchak10Andrzej Gzella11Krzysztof Bielawski12Anna Bielawska13Rostyslav Stoika14Roman Lesyk15Institute of Cell Biology of National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, UkraineDepartment of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, UkraineDepartment of Biotechnology, Faculty of Pharmacy, Medical University of Bialystok, 15-089 Bialystok, PolandInstitute of Cell Biology of National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, UkraineInstitute of Cell Biology of National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, UkraineDepartment of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, UkraineDepartment of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, UkraineDepartment of Synthesis and Technology of Drugs, Faculty of Pharmacy, Medical University of Bialystok, 15-089 Bialystok, PolandInstitute of Cell Biology of National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, UkraineDepartment of Organic Chemistry, Medical University of Lublin, Aleje Racławickie 1, 20-059 Lublin, PolandInstitute of Cell Biology of National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, UkraineDepartment of Organic Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, PolandDepartment of Synthesis and Technology of Drugs, Faculty of Pharmacy, Medical University of Bialystok, 15-089 Bialystok, PolandDepartment of Biotechnology, Faculty of Pharmacy, Medical University of Bialystok, 15-089 Bialystok, PolandInstitute of Cell Biology of National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, UkraineDepartment of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, UkraineNovel 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 <b>3</b> and 4-(2-{1-(2-fluorophenyl)-3-[4-methyl-2-(pyridin-2-ylamino)-thiazol-5-yl]-3-oxopropylsulfanyl}-acetylamino)-benzoic acid ethyl ester <b>4</b> was revealed. The IC<sub>50</sub> of the compound <b>3</b> in HL-60 cells of the acute human promyelocytic leukemia was 0.57 µM, while in the pseudo-normal human cell lines, the IC<sub>50</sub> of this compound was >50 µM, which suggests that the compounds <b>3</b> and <b>4</b> might be perspective anticancer agents. The detected selectivity of the derivatives <b>3</b> and <b>4</b> 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 <b>3</b> and <b>4</b> 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.https://www.mdpi.com/1420-3049/27/19/6219drug developmentthiazolescancertumor cellsPARP |
| spellingShingle | Iryna Ivasechko Ihor Yushyn Piotr Roszczenko Julia Senkiv Nataliya Finiuk Danylo Lesyk Serhii Holota Robert Czarnomysy Olga Klyuchivska Dmytro Khyluk Nataliya Kashchak Andrzej Gzella Krzysztof Bielawski Anna Bielawska Rostyslav Stoika Roman Lesyk Development of Novel Pyridine-Thiazole Hybrid Molecules as Potential Anticancer Agents Molecules drug development thiazoles cancer tumor cells PARP |
| title | Development of Novel Pyridine-Thiazole Hybrid Molecules as Potential Anticancer Agents |
| title_full | Development of Novel Pyridine-Thiazole Hybrid Molecules as Potential Anticancer Agents |
| title_fullStr | Development of Novel Pyridine-Thiazole Hybrid Molecules as Potential Anticancer Agents |
| title_full_unstemmed | Development of Novel Pyridine-Thiazole Hybrid Molecules as Potential Anticancer Agents |
| title_short | Development of Novel Pyridine-Thiazole Hybrid Molecules as Potential Anticancer Agents |
| title_sort | development of novel pyridine thiazole hybrid molecules as potential anticancer agents |
| topic | drug development thiazoles cancer tumor cells PARP |
| url | https://www.mdpi.com/1420-3049/27/19/6219 |
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