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

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.