Background: The development of novel antineoplastic agents remains highly desirable.
Objective: This study focuses on the design, synthesis, and antitumor evaluation of phenyl ureas
bearing 5-fluoroindolin-2-one moiety.
Methods: Three sets of phenylureas were designed and synthesized and their antiproliferative ability
was measured against four human carcinoma cell lines (Hela, Eca-109, A549, and MCF-7) via
MTT assay. In vivo anticancer activity was further evaluated in xenograft models of human breast
Results: A total of twenty-one new compounds were synthesized and characterized by means of
1H and 13C NMR as well as HR-MS. Three sets of compounds (1a‒1c, 2a‒2c, and 3a‒3c) were initially
constructed, and preliminary antiproliferative activities of these molecules were evaluated
against Hela, Eca-109, A549 and MCF-7, highlighting the meta-substituted phenylureas (1a‒1c) as
the most cytotoxic set. A series of meta-substituted phenylureas derivatives (1d‒1o) were then designed
and synthesized for structure-activity relationship study. Most of the new compounds
showed desirable cytotoxicity, among which compound 1g exhibited the most remarkable cytotoxic
effects against the tested human cancer cells with IC50 values ranging from 1.47 to 6.79 μM.
Further studies showed that compound 1g suppressed tumor growth in human breast cancer (MCF-
7) xenograft models without affecting the body weight of its recipients.
Conclusion: In this study, twenty-one new compounds, containing the privileged structures of
phenylurea and 5-fluoroindolin-2-one, were designed and synthesized. Subsequent structureactivity
studies showed that 1g was the most bioactive antitumor agent among all tested compounds,
hence a potentially promising lead compound once given further optimization.