Design, Synthesis and Preliminary Biological Evaluation of Novel Benzyl Sulfoxide 2-Indolinone Derivatives as Anticancer Agents

Abstract

In this work, a series of novel benzyl sulfoxide 2-indolinone derivatives was designed and synthesized as potent anticancer agents. Tyrosine kinase inhibitory activity assay indicated that most of the compounds showed significant activity. The in vitro antiproliferative activity of these compounds was further investigated against five human cancer cell lines (HeLa, HepG2, MCF-7, SCC-15, and A549). Several compounds exhibited evident activities. Among them, (Z)-3-(((4-bromobenzyl)sulfinyl)methylene)indolin-2-one (6j) and (Z)-3-((benzylsulfinyl)methylene)-5-bromoindolin-2-one (6o) were found to be effective tyrosine kinase inhibitors (IC50 = 1.34 and 2.69 μM, respectively) in addition to having noteworthy antitumor potential (the average IC50 value of 6j or 6o was less than 40 μM). This class of novel derivatives has promising potential for further development as anticancer agents.

Synthesis and antitumor effects of novel benzyl naphthyl sulfoxide/sulfone derivatives derived from Rigosertib

“…The cytotoxicity of them was measured by MTS tetrazolium assay. 29 Rigosertib was used as the positive control. The IC 50 values for each compound are summarized in Table 1 .…”

Design, Synthesis and Preliminary Biological Evaluation of Benzylsulfone Coumarin Derivatives as Anti-Cancer Agents

“…Total cell lysates were immunoprecipitated with anti-PI3K antibody, and PI3K activity was assessed by ELISA. Finally, the kinase assay was detected at 450 nm with microplate reader and the inhibition rate was calculated using the following equation [46].…”

An overview on 2-indolinone derivatives as anticancer agents

“…4) 12 and benzyl Sulfoxide 2-indolinone derivatives; PHA665752 and SU11274 (Fig. 4) 14 will be handled in details.…”

“…22 It can be obtained by reaction of 5-fluorooxindole and from Vilsmeier adduct (Scheme 4). 14,23 Scheme 4. Synthesis of sunitinib.…”