1608152-61-9Relevant academic research and scientific papers
Bis-arylidene oxindoles as anti-breast-cancer agents acting via the estrogen receptor
Pal, Abhishek,Ganguly, Anirban,Ghosh, Avijit,Yousuf, Md,Rathore, Bhowmira,Banerjee, Rajkumar,Adhikari, Susanta
, p. 727 - 732 (2014/05/06)
We report a new family of bis-arylidene oxindole derivatives that show highly selective estrogen receptor (ER)-mediated anticancer activity at low-nanomolar concentrations in ER-positive (ER+) breast cancer cells. In terms of cell growth inhibition, IC50 values for these compounds in ER+ breast cancer cells are two to three orders of magnitude lower than in ER-negative (ER-) breast cancer cells and non-cancer cells. In comparison with known bis-arylidene drugs, these compounds are at least three orders of magnitude more toxic than tamoxifen and 1.5-4-fold more toxic than 4-hydroxytamoxifen in ER+ MCF-7 cancer cells. These oxindoles inhibit ER transactivation, and their anticancer activities are inhibited in ER-depleted MCF-7 cells. Some of these nonsteroidal molecules also exhibit essential properties of selective ER down-regulation. From the development of two series of bis-arylidene oxindole-based compounds, we report a new series of anticancer agents for estrogen-responsive breast cancer. A trip to the ER: We developed oxindole derivatives that exhibit anticancer activity at low-nanomolar IC 50 concentrations (30-70 nM) against ER-positive breast cancer cells. Results of siRNA studies reveal that the anticancer effects of these molecules are mediated by the estrogen receptor (ER). These compounds also inhibit ER-mediated transactivation and exhibit selective ER modulating and down-regulating properties.
