Vanillin-Based Indolin-2-one Derivative Bearing a Pyridyl Moiety as a Promising Anti-Breast Cancer Agent via Anti-Estrogenic Activity
Onur Bender, İsmail Çeli̇k, Rumeysa Dogan, Arzu Atalay, Mai E. Shoman, Taha F. S. Ali, Eman A. M. Beshr, Mahmoud H. Mohamed, Eman Alaaeldin, Ahmed M. Shawky, Eman M. Awad, Al‐Shaimaa F. Ahmed, Kareem M. Younes, Mukhtar Ansari, Sirajudheen Anwar
Abstract
High Resolution Image Download MS PowerPoint Slide The structure-based design introduced indoles as an essential motif in designing new selective estrogen receptor modulators employed for treating breast cancer. Therefore, here, a series of synthesized vanillin-substituted indolin-2-ones were screened against the NCI-60 cancer cell panel followed by in vivo, in vitro, and in silico studies. Physicochemical parameters were evaluated with HPLC and SwissADME tools. The compounds demonstrated promising anti-cancer activity for the MCF-7 breast cancer cell line (GI = 6–63%). The compound with the highest activity ( 6j ) was selective for the MCF-7 breast cancer cell line (IC 50 = 17.01 μM) with no effect on the MCF-12A normal breast cell line supported by real-time cell analysis. A morphological examination of the used cell lines confirmed a cytostatic effect of compound 6j . It inhibited both in vivo and in vitro estrogenic activity, triggering a 38% reduction in uterine weight induced by estrogen in an immature rat model and hindering 62% of ER-α receptors in in vitro settings. In silico molecular docking and molecular dynamics simulation studies supported the stability of the ER-α and compound 6j protein–ligand complex. Herein, we report that indolin-2-one derivative 6j is a promising lead compound for further pharmaceutical formulations as a potential anti-breast cancer drug.