Synthesis and Antiproliferative Activity of Isolongifolanone Pyrazoline Derivatives Inducing Intracellular ROS Accumulation

Abstract

A series of new isolongifolanone pyrazoline derivatives were synthesized and characterized by 1H NMR and HRMS methods. The compounds were assessed for their antiproliferative activity against three cancer cell lines (MDA-MB-231, Hela, and HepG2 cells) in vitro. Most of the derivatives showed considerable cytotoxic activity to all three cancer cell lines. Among them, compound 400 exhibited excellent antiproliferative activity with IC₅₀ values of 15.45, 18.52, and 34.4 μM for MDA-MB-231, Hela, and HepG2 cells, respectively. Further mechanistic studies indicated that compound 400 induced apoptosis in HepG2 cells by enhancing the accumulation of intracellular reactive oxygen species (ROS). In summary, we report the synthesis of a new pyrazoline derivative of isolongifolanone (compound 400) that potently induces apoptosis in HepG2 cells by enhancing intracellular ROS production.