Novel antitumor compound optimized from natural saponin Albiziabioside A induced caspase-dependent apoptosis and ferroptosis as a p53 activator through the mitochondrial pathway

European Journal of Medicinal Chemistry
Gaofei WeiYang Liu

Abstract

It is highly desirable to activation p53 function with small-molecule compounds for colon cancer therapy. Triterpene saponin has been characterized with the favorable selectivity and safety profiles. However, the application of triterpene saponin as cancer chemotherapy drugs was hampered primarily by moderate anticancer potency and the lack the mechanism of action. In this study, we synthesized a series of Albiziabioside A derivatives and evaluated the antitumor activity both in vitro and in vivo. Compounds D13 possessed strong inhibitory activity against HCT116 cells with IC50 values of 5.19 μM. More importantly, compound D13 had a favorable selectivity and was efficacious against MDR cancer cells. Moreover, compound D13 could induce apoptosis and ferroptosis through the mitochondrial pathway as a p53 activator. In addition, compound D13 significantly suppressed tumorigenesis without inducing toxicity in normal organs in vivo. Collectively, this study provides a clinically relevant argument for considering triterpene saponin derivatives D13 as potential cancer therapeutic candidates with enhanced activity, acceptable safety and novel mechanisms of action. To the best of our knowledge, this compound is the first drug candidate ...Continue Reading

Citations

Jul 11, 2019·Dalton Transactions : an International Journal of Inorganic Chemistry·Taj-Malook KhanZhen-Feng Chen
Aug 14, 2019·Oncology Letters·Yan SongBang-Mao Wang
Sep 5, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zhan-Fang FanMao-Sheng Cheng
Apr 8, 2020·Frontiers in Pharmacology·Chu HanBo Li
Nov 14, 2020·International Journal of Molecular Sciences·Juan LiuZhaohui Feng
Mar 17, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Junting XiaoChengzhi Chen
Mar 31, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Kai ZhengZhendan He
Apr 28, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Kaichun WangDaode Hu
Jan 29, 2022·Cell Death and Differentiation·Yanqing Liu, Wei Gu

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