New Anticancer Agents: Design, Synthesis, Biological Activity, and Molecular Docking of Bicyclic Phloroglucinol Derivatives

Abstract Bicyclic phloroglucinol is a phenolic compound which mainly exist in Dryopteris fragrans (L.) Schott with antiinflammatory, antithrombotic, antifungal and antitumor activity. Although a series of anticancer agents target various tumors under clinical trials, different limitations hinder their clinical development and novel targeting chemical agents are required. Herein, we have made a number of modifications around the scaffold of the phloroglucinol. The results of antitumor activities reveal that compound A5 against A549 cells and compound A3 against HepG2 and McF‐7 cells were best with a degree of concentration dependence, which stronger than that of positive control 5‐FU, and compound A3 and A5 display lower cytotoxicity to normal cells. The molecule docking studies indicate protein Bcl‐xl and Mcl‐12 may be a potential target of these compounds. In general, A3 and A5 with potent binding affinity and good efficacy have the potential to develop into antitumor lead compounds which also deserve further study.