Synthesis of 3-O-Acetyl-11-keto-β-boswellic Acid (AKBA)-Derived Amides and Their Mitochondria-Targeted Antitumor Activities

[Image: see text] In this study, we synthesized a series of amide and mitochondria-targeted derivatives with 3-O-acetyl-11-keto-β-boswellic acid (AKBA) as the parent structure and an ethylenediamine moiety as the link chain. Compound 5e, a mitochondrial-targeting potential derivative, showed significantly stronger antitumor activity than that of AKBA, and it could induce vacuolization of A549 cells and stimulate the production of reactive oxygen species (ROS) in a time- and concentration-dependent manner. The antioxidant N-acetylcysteine (NAC) could inhibit the ROS level but could not suppress vacuolization and cell death induced by 5e. Further studies demonstrated that 5e caused abnormal opening of mitochondrial permeability transition pore (MPTP) and a decrease of mitochondrial membrane potential; additionally, it caused cell cycle arrest in G(0)/G(1) but did not induce apoptosis. 5e represented a compound with improved antiproliferative effects for cancer therapy working through new mechanisms.