第十五届海洋药物学术年会暨2021国际海洋药物研讨会

15 / 2021-10-08 19:48:01

Cyclometalatediridium-β-carboline complexes induce mitochondria-targeted apoptosis

mitochondria-targeted,cyclometalated iridium-β-carboline complexes

    Marine natural products are important source of compounds having anti-tumor activities, and β-carboline skeleton is one of the most intriguing indolebased heterocycles, its basic ring system being found in many natural products and pharmaceutical drugs. These compounds are of great interest due to their good biological activities, such as antitumor, antiparasitic, antibacterial, and antiviral activities. We synthesized β-carboline derivatives and structurally modified them to be further attached to iridium metal centers. The cyclometalated iridium-β-carboline complexes were taken up by human lung adenocarcinoma A549 cells very quickly and specifically targeted mitochondria. They induced a series of mitochondria-related dysfunctional events, including the loss of mitochondrial membrane potential, cellular ATP depletion and reactive oxygen species (ROS) elevation, which lead to the damage of mitochondria and then the mitochondria-targeted apoptosis.