Design, Synthesis, and Biological Activity of Marinacarboline Analogues as STAT3 Pathway Inhibitors for Docetaxel-Resistant Triple-Negative Breast Cancer.

Metastatic triple-negative breast cancer (mTNBC) is a fatal type of breast cancer (BC), and signal transducer and activator of transcription 3 (STAT3) has emerged as an effective target for mTNBC. In the present study, compound was found to be a novel synthetic STAT3 pathway inhibitor, and its potential antitumor activity was demonstrated using and models in docetaxel-resistant TNBC cells. Based on marinacarboline (MC), a series β-carboline derivatives were synthesized and investigated for their antitumor activities against docetaxel-resistant MDA-MB-231 (MDA-MB-231-DTR) cells. Combining antiproliferation and STAT3 inhibitory activities, was selected as the most promising β-carboline compound. effectively impeded the metastatic potential of MDA-MB-231-DTR cells , and the combination of and docetaxel exhibited potent antitumor activities in a xenograft mouse model. These findings suggested that can be a lead candidate as a target therapeutic agent for TNBC patients with docetaxel resistance.