Mitochondria-targeted triphenylphosphonium conjugated glycyrrhetinic acid derivatives as potent anticancer drugs |
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Affiliation: | 1. School of Materials Science and Engineering, Henan Polytechnic University, Jiaozuo 454003, PR China;2. Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), Nanjing 211816, PR China;3. Institute of Flexible Electronics (IFE), Northwestern Polytechnical University (NPU), Xi''an 710072, PR China;4. Institute of Photonics Technology, Jinan University, Guangzhou 510632, PR China;5. School of Physical Science and Technology, Lanzhou University, Lanzhou 730000, PR China |
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Abstract: | Glycyrrhetinic acid has been usually studied for their anti-tumor activities. However, the low bioavailability and poor aqueous solubility as well as limited intracellular accumulation have limited their utility. In this present study, a series of new glycyrrhetinic acid conjugates with a triphenylphosphonium cation (TTP+) moiety, meant to specifically target them to tumor cells mitochondria, have been designed and synthesized. Among them, compound 2f possessed excellent antitumor activities against the tested human cancer cells, and simultaneously exhibited better cell selectivity between cancer cells and normal cells than glycyrrhetinic acid and HCPT. Moreover, 2f significantly induced cell cycle arrest at the G2/M phase, and effectively inhibited cancer cells proliferation and migration. Mechanism studies revealed that 2f triggered apoptosis through the mitochondrial pathway via the collapse of mitochondrial membrane potential, reactive oxygen species production and the activation of caspase-9 and caspase-3. |
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Keywords: | Glycyrrhetinic acid Anti-tumor Mitochondria Apoptosis |
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