Design, synthesis, molecular docking and anticancer activity evaluation of methyl salicylate based thiazoles as PTP1B inhibitors
Abstract This work presents a rational synthesis of 14 innovative methyl salicylate based thiazole (MSBT) derivatives, designed as protein tyrosine phosphatase 1B (PTP1B) inhibitors with potent anticancer activity. Enzyme inhibition studies were performed for all compounds. In addition, molecular do...
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Nature Portfolio
2025-02-01
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| Online Access: | https://doi.org/10.1038/s41598-025-88038-9 |
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| author | Dominika Kołodziej-Sobczak Łukasz Sobczak Wojciech Płaziński Adrianna Sławińska-Brych Magdalena Mizerska-Kowalska Klaudia Hołub Barbara Zdzisińska Karol Jaroch Barbara Bojko Krzysztof Z. Łączkowski |
| author_facet | Dominika Kołodziej-Sobczak Łukasz Sobczak Wojciech Płaziński Adrianna Sławińska-Brych Magdalena Mizerska-Kowalska Klaudia Hołub Barbara Zdzisińska Karol Jaroch Barbara Bojko Krzysztof Z. Łączkowski |
| author_sort | Dominika Kołodziej-Sobczak |
| collection | DOAJ |
| description | Abstract This work presents a rational synthesis of 14 innovative methyl salicylate based thiazole (MSBT) derivatives, designed as protein tyrosine phosphatase 1B (PTP1B) inhibitors with potent anticancer activity. Enzyme inhibition studies were performed for all compounds. In addition, molecular docking simulations and assessment of antiproliferative activity were performed for the most active of the lot. For antiproliferative studies, the cell lines of breast cancer (T47D) and non-small-cell lung carcinoma (A549), as well as healthy control of human skin fibroblasts (HSF), were used. As a result, 3 compounds were found to inhibit the PTP1B enzyme in submicromolar concentrations: 3j (IC50 = 0.51 ± 0.15 µM), 3f. (IC50 = 0.66 ± 0.38 µM) and 3d (IC50 = 0.93 ± 0.51 µM), all surpassing the reference inhibitor as much as sixfold (IC50 = 3.23 ± 0.85 µM). Moreover, compound 3j was found to be highly selective towards T47D cancer cells. The cellular mechanism of compound 3j action was associated with the inhibition of DNA replication via blocking the S phase of interphase and induction of apoptosis. Also, molecular docking simulations made for compound 3j revealed continuous interactions between the molecule and the catalytic site, as well as with all the loops involved in the catalytic activity of the protein. Therefore, the new group of MSBT derivatives offers great promise for safe and effective anticancer therapy. |
| format | Article |
| id | doaj-art-83fcfcae773f4cb38461c3e4ce0e6d2a |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-83fcfcae773f4cb38461c3e4ce0e6d2a2025-08-20T02:12:58ZengNature PortfolioScientific Reports2045-23222025-02-0115111510.1038/s41598-025-88038-9Design, synthesis, molecular docking and anticancer activity evaluation of methyl salicylate based thiazoles as PTP1B inhibitorsDominika Kołodziej-Sobczak0Łukasz Sobczak1Wojciech Płaziński2Adrianna Sławińska-Brych3Magdalena Mizerska-Kowalska4Klaudia Hołub5Barbara Zdzisińska6Karol Jaroch7Barbara Bojko8Krzysztof Z. Łączkowski9Department of Chemical Technology and Pharmaceuticals, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus UniversityHospital Pharmacy, Multidisciplinary Municipal Hospital in BydgoszczJerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of SciencesDepartment of Cell Biology, Institute of Biological Sciences, Maria Curie-Skłodowska UniversityDepartment of Virology and Immunology, Institute of Biological Sciences, Maria Curie-Skłodowska UniversityDepartment of Virology and Immunology, Institute of Biological Sciences, Maria Curie-Skłodowska UniversityDepartment of Virology and Immunology, Institute of Biological Sciences, Maria Curie-Skłodowska UniversityDepartment of Pharmacodynamics and Molecular Pharmacology, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus UniversityDepartment of Pharmacodynamics and Molecular Pharmacology, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus UniversityDepartment of Chemical Technology and Pharmaceuticals, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus UniversityAbstract This work presents a rational synthesis of 14 innovative methyl salicylate based thiazole (MSBT) derivatives, designed as protein tyrosine phosphatase 1B (PTP1B) inhibitors with potent anticancer activity. Enzyme inhibition studies were performed for all compounds. In addition, molecular docking simulations and assessment of antiproliferative activity were performed for the most active of the lot. For antiproliferative studies, the cell lines of breast cancer (T47D) and non-small-cell lung carcinoma (A549), as well as healthy control of human skin fibroblasts (HSF), were used. As a result, 3 compounds were found to inhibit the PTP1B enzyme in submicromolar concentrations: 3j (IC50 = 0.51 ± 0.15 µM), 3f. (IC50 = 0.66 ± 0.38 µM) and 3d (IC50 = 0.93 ± 0.51 µM), all surpassing the reference inhibitor as much as sixfold (IC50 = 3.23 ± 0.85 µM). Moreover, compound 3j was found to be highly selective towards T47D cancer cells. The cellular mechanism of compound 3j action was associated with the inhibition of DNA replication via blocking the S phase of interphase and induction of apoptosis. Also, molecular docking simulations made for compound 3j revealed continuous interactions between the molecule and the catalytic site, as well as with all the loops involved in the catalytic activity of the protein. Therefore, the new group of MSBT derivatives offers great promise for safe and effective anticancer therapy.https://doi.org/10.1038/s41598-025-88038-9Protein tyrosine phosphatase 1BEnzyme inhibitorMolecular docking |
| spellingShingle | Dominika Kołodziej-Sobczak Łukasz Sobczak Wojciech Płaziński Adrianna Sławińska-Brych Magdalena Mizerska-Kowalska Klaudia Hołub Barbara Zdzisińska Karol Jaroch Barbara Bojko Krzysztof Z. Łączkowski Design, synthesis, molecular docking and anticancer activity evaluation of methyl salicylate based thiazoles as PTP1B inhibitors Scientific Reports Protein tyrosine phosphatase 1B Enzyme inhibitor Molecular docking |
| title | Design, synthesis, molecular docking and anticancer activity evaluation of methyl salicylate based thiazoles as PTP1B inhibitors |
| title_full | Design, synthesis, molecular docking and anticancer activity evaluation of methyl salicylate based thiazoles as PTP1B inhibitors |
| title_fullStr | Design, synthesis, molecular docking and anticancer activity evaluation of methyl salicylate based thiazoles as PTP1B inhibitors |
| title_full_unstemmed | Design, synthesis, molecular docking and anticancer activity evaluation of methyl salicylate based thiazoles as PTP1B inhibitors |
| title_short | Design, synthesis, molecular docking and anticancer activity evaluation of methyl salicylate based thiazoles as PTP1B inhibitors |
| title_sort | design synthesis molecular docking and anticancer activity evaluation of methyl salicylate based thiazoles as ptp1b inhibitors |
| topic | Protein tyrosine phosphatase 1B Enzyme inhibitor Molecular docking |
| url | https://doi.org/10.1038/s41598-025-88038-9 |
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