Synthesis, Characterization and in vitro Anticancer Evaluation of 5-Sulfinyl(sulfonyl)-4-arylsulfonyl-Substituted 1,3-Oxazoles.

Autor: Zyabrev V; Department of Chemistry of Bioactive Nitrogen-Containing Heterocyclic Bases, V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine, Academician Kukhar st. 1, 02094, Kyiv, Ukraine., Pilyo S; Department of Chemistry of Bioactive Nitrogen-Containing Heterocyclic Bases, V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine, Academician Kukhar st. 1, 02094, Kyiv, Ukraine., Demydchuk B; Department of Chemistry of Bioactive Nitrogen-Containing Heterocyclic Bases, V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine, Academician Kukhar st. 1, 02094, Kyiv, Ukraine., Kachaeva M; Department of Chemistry of Bioactive Nitrogen-Containing Heterocyclic Bases, V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine, Academician Kukhar st. 1, 02094, Kyiv, Ukraine., Semenyuta I; Department of Biomedical Research, V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine, Academician Kukhar st. 1, 02094, Kyiv, Ukraine., Zhirnov V; Department of Chemistry of Bioactive Nitrogen-Containing Heterocyclic Bases, V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine, Academician Kukhar st. 1, 02094, Kyiv, Ukraine., Velihina Y; Department of Chemistry of Bioactive Nitrogen-Containing Heterocyclic Bases, V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine, Academician Kukhar st. 1, 02094, Kyiv, Ukraine.; Laboratoire COBRA, INSA Rouen Normandie, Bâtiment IRCOF, rue Tesnière 1, 76821, Mont Saint-Aignan Cedex, France., Brovarets V; Department of Chemistry of Bioactive Nitrogen-Containing Heterocyclic Bases, V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine, Academician Kukhar st. 1, 02094, Kyiv, Ukraine.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2023 Jul 17; Vol. 18 (14), pp. e202300161. Date of Electronic Publication: 2023 May 24.
DOI: 10.1002/cmdc.202300161
Abstrakt: A novel series of 5-sulfinyl(sulfonyl)-4-arylsulfonyl-substituted 1,3-oxazoles has been synthesized, characterized and subjected to NCI in vitro assessment. Cancer cell lines of all subpanels were most sensitive to 2-{[4-[(4-fluorophenyl)sulfonyl]-2-(2-furyl)-1,3-oxazol-5-yl]sulfinyl}acetamide (3 l). Its antiproliferative and cytotoxic activity averaged over each subpanel was manifested in a very narrow range of concentrations (GI 50 : 1.64-1.86 μM, TGI: 3.16-3.81 μM and LC 50 : 5.53-7.27 μM), i. e. practically did not depend on the origin of the cancer cell line. The COMPARE matrix using TGI vector showed a high positive correlation of 3 l (r=0.88) with the intercalating agent aclarubicin, which inhibits topoisomerases. The absence in the database of standard agents that have a high correlation with the cytotoxicity of this compound suggests that it may have a unique mechanism of action. According to the results of the docking analysis, the most promising anticancer target for compound 3 l is DNA topoisomerase IIβ. The obtained results indicate the anticancer activity of 5-sulfinyl(sulfonyl)-4-arylsulfonyl-substituted 1,3-oxazoles, which may be useful for the development of new anticancer drugs. 2-{[4-[(4-Fluorophenyl)sulfonyl]-2-(2-furyl)-1,3-oxazol-5-yl]sulfinyl}acetamide (3 l), as the most active, can be recommended for further in-depth studies.
(© 2023 The Authors. ChemMedChem published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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