Discovery of Alkyl Triphenylphosphonium Pinostrobin Derivatives as Potent Anti‐Breast Cancer Agents

Abstract

Pinostrobin demonstrated anticancer properties, but its hydrophobic feature led to a reduction in bioavailability. The mitochondria‐targeted approach successfully synthesized eight new alkyl triphenylphosphonium pinostrobin derivatives (1–8) with good yield in this study. Seven compounds (1–3, 5–8) showed greater cytotoxic potency against the human MCF‐7 breast cancer cell line than pinostrobin. Molecular docking studies were performed with two important targets in hormone‐dependent anticancer strategies, estrogen receptor α (ERα) ligand binding domains, 3ERT (antagonist recognition and antiproliferative function), and 1GWR (agonist recognition and pro‐proliferative function). In addition, the MD simulation study of the two most potent compounds (2 and 3) complexed with both ERα forms suggested that compounds 2 and 3 could serve as favourable antagonists. Furthermore, the in silico ADMET prediction indicated that compounds 2 and 3 could be potential drug candidates.