Virtual screening for triple-negative breast cancer cell inhibitors based on telomere G-quadruplex structure

Abstract

Triple-negative breast cancer is an aggressive subtype that frequently develops resistance to chemotherapy. It is expected to develop new anti-tumor drugs through targeting the structure of G-quadruplexes of the genes associated with this tumor. In this work, by targeting the 21-mer telomere G-quadruplex structure, compounds VB07 and VC02 were identified to stabilize the telomere G-quadruplex through structure-based high-throughput virtual screening. Cell cytotoxicity assay showed that VB07 and VC02 exhibited inhibitory effect on triple-negative breast cancer cells at the concentration of 5 μM. This study showed that structure-based high-throughput virtual screening was able to successfully identify the proper compounds targeting the telomere G-quadruplex, which exhibited inhibitory effects against the triple-negative breast cancer cells.