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

Abstract

AbstractA 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 (GI50: 1.64–1.86 μM, TGI: 3.16–3.81 μM and LC50: 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.