Targeting triple-negative breast cancers : discovery of novel lead compounds and their biological characterziation

Abstract

Triple-negative breast cancer (TNBC) is highly aggressive and lacks effective targeted treatments due to the absence of key receptors. This dissertation explores novel compounds from the Leibniz Institute of Plant Biochemistry to identify potential TNBC therapies. Initially, poly(ADP-ribose) polymerase inhibitors (PARPi) were studied, revealing a quinazolinone derivative with five-fold higher PARP-1 inhibition than olaparib’s core structure. Additionally, azaglycophymines showed anticancer activity but lacked TNBC selectivity. The most promising discovery was selectAHRyl A, a prodrug selectively activating the AHR pathway in TNBC. This research expands TNBC treatment options and lays the foundation for further drug development.