1. Discovery of Alkyl Triphenylphosphonium Pinostrobin Derivatives as Potent Anti-Breast Cancer Agents.
- Author
-
Tran TH, Le TH, Nguyen TT, Vong LB, Nguyen MTT, Nguyen NT, and Dang PH
- Subjects
- Humans, Structure-Activity Relationship, MCF-7 Cells, Estrogen Receptor alpha metabolism, Estrogen Receptor alpha antagonists & inhibitors, Female, Drug Discovery, Molecular Structure, Dose-Response Relationship, Drug, Flavanones, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents chemical synthesis, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Breast Neoplasms metabolism, Molecular Docking Simulation, Cell Proliferation drug effects, Drug Screening Assays, Antitumor, Organophosphorus Compounds chemistry, Organophosphorus Compounds pharmacology, Organophosphorus Compounds chemical synthesis
- 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., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)
- Published
- 2024
- Full Text
- View/download PDF