The 5-hydrazino-3-methylisothiazole-4-carboxylic acid, its new 5-substituted derivatives and their antiproliferative activity
| Autor: | Justyna Trynda, Izabela Jęśkowiak, Marcin Mączyński, Stanisław Ryng, Joanna Wietrzyk |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Stereochemistry
Colorectal cancer Carboxylic acid Carboxylic Acids Antineoplastic Agents 01 natural sciences Biochemistry Structure-Activity Relationship chemistry.chemical_compound Drug Discovery medicine Humans Doxorubicin Molecular Biology Cells Cultured Cell Proliferation chemistry.chemical_classification Isothiazole Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Organic Chemistry Combination chemotherapy Nuclear magnetic resonance spectroscopy Carbon-13 NMR medicine.disease 0104 chemical sciences Thiazoles 010404 medicinal & biomolecular chemistry chemistry Proton NMR Drug Screening Assays Antitumor medicine.drug |
| Zdroj: | Bioorganic Chemistry. 91:103082 |
| ISSN: | 0045-2068 |
| DOI: | 10.1016/j.bioorg.2019.103082 |
| Popis: | Currently, the basic method of treatment of colon cancer is surgery. The range of anticancer drugs used in the treatment of colorectal cancer is small and is based mainly on systemic combination chemotherapy. As a result of the designed syntheses, we received new isothiazole derivatives with anticancer activity. The synthesized 5-hydrazino-3-methylisothiazole-4-carboxylic acid has never been obtained before. It is also a substrate for the synthesis of its innovative derivatives, i.e. compounds that are Schiff bases. The identification of the structure of new compounds was carried out using mass spectrometry (MS), proton nuclear magnetic resonance spectroscopy ( 1 H NMR), carbon nuclear magnetic resonance spectroscopy ( 13 C NMR) and infrared spectroscopy (IR). Potential antitumor activity was confirmed in antiproliferative MTT and SRB tests. The selected, most biologically active substances were characterized by high selectivity towards leukemia and colon cancer cell lines. They caused high inhibition of proliferation of human biphenotypic B cell myelomonocytic leukemia MV4-11 (13 compounds), human colon adenocarcinoma cell lines sensitive LoVo (8 compounds) and resistant to doxorubicin LoVo/DX (12 compounds). However, in the conducted studies, their activity against breast adenocarcinoma MCF-7 and normal non-tumorigenic epithelial cell line derived from mammary gland MCF-10A was substantially lower. The result of this work is claimed Polish patent application. |
| Databáze: | OpenAIRE |
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