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  3. Design, synthesis, molecular docking and anticancer activity evaluation of methyl salicylate based thiazoles as PTP1B inhibitors

Design, synthesis, molecular docking and anticancer activity evaluation of methyl salicylate based thiazoles as PTP1B inhibitors

  • Sci Rep. 2025 Feb 10;15(1):4892. doi: 10.1038/s41598-025-88038-9.
Dominika Kołodziej-Sobczak 1,  Łukasz Sobczak 2,  Wojciech Płaziński 3 4,  Adrianna Sławińska-Brych 5,  Magdalena Mizerska-Kowalska 6,  Klaudia Hołub 6,  Barbara Zdzisińska 6,  Karol Jaroch 7,  Barbara Bojko 7,  Krzysztof Z Łączkowski 8
Affiliations

Affiliations

  • 1 Department of Chemical Technology and Pharmaceuticals, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Jurasza 2, 85-089, Bydgoszcz, Poland. d.kolodziejsobczak@cm.umk.pl.
  • 2 Hospital Pharmacy, Multidisciplinary Municipal Hospital in Bydgoszcz, Szpitalna 19, 85-826, Bydgoszcz, Poland.
  • 3 Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Niezapominajek 8, 30-239, Kraków, Poland.
  • 4 Department of Biopharmacy, Medical University of Lublin, Chodźki 4A, 20-093, Lublin, Poland.
  • 5 Department of Cell Biology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, 20-033, Lublin, Poland.
  • 6 Department of Virology and Immunology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, 20-033, Lublin, Poland.
  • 7 Department of Pharmacodynamics and Molecular Pharmacology, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Jurasza 2, 85-089, Bydgoszcz, Poland.
  • 8 Department of Chemical Technology and Pharmaceuticals, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Jurasza 2, 85-089, Bydgoszcz, Poland.
PMID: 39929933 DOI: 10.1038/s41598-025-88038-9
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.

Keywords

Enzyme inhibitor; Molecular docking; Protein tyrosine phosphatase 1B.

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