Synthesis and biological evaluation of s‐, o‐ and se‐containing dispirooxindoles

Abstract

A series of novel S‐, O‐ and Se‐containing dispirooxindole derivatives has been synthesized using 1,3‐dipolar cycloaddition reaction of azomethine ylide generated from isatines and sarcosine at the double C=C bond of 5‐indolidene‐2‐chalcogen‐imidazolones (chalcogen was oxygen, sulfur or selenium). The cytotoxicity of these dispiro derivatives was evaluated in vitro using different tumor cell lines. Several molecules have demonstrated a considerable cytotoxicity against the panel and showed good selectivity towards colorectal carcinoma HCT116 p53+/+ over HCT116 p53−/− cells. In particular, good results have been obtained for LNCaP prostate cell line. The performed in silico study has revealed MDM2/p53 interaction as one of the possible targets for the synthesized molecules. However, in contrast to selectivity revealed during the cell‐based evaluation and the results obtained in computational study, no significant p53 activation using a reporter construction in p53wt A549 cell line was observed in a relevant concentration range.