Rational Design, Synthesis and Biological Evaluation of Indolinone-based Small Molecules Targeting Breast Cancer

Summary

Breast cancer is the most frequent malignancy in women worldwide. Discovery and development of small molecules that can efficiently interact with the overexpressed proteins responsible for the development and progression of breast cancer is the key focus of our work. Indolin-2-one scaffold is considered a privileged scaffold present in medicinally useful natural and synthetic compounds. Available literatures show promising therapeutic efficacy exhibited by this scaffold in in vitro and in vivo breast cancer models. We previously reported a set of indolinone-based compounds with nanomolar activity against MDA-MB-468 breast cancer cell line via targeting Aurora B kinase enzyme which presented a promising candidate for further development to target breast cancer.

In continuation of our work, we aim to investigate the structure-activity relationship (SAR) of these derivatives and to optimize their activity against breast cancer cell lines as MCF-7 and MDA-MB-468. In addition, we seek to investigate their mechanism of action in details, to establish these derivatives potency in vivo, and to demonstrate their safety and selectivity. Our final aim is to develop a preclinical candidate to target breast cancer.

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