The Configuration-Dependent Anti-Leukemic Effect of Manoalide Stereoisomers: Reignite Research Interest in these Sponge-Derived Sesterterpenoids

Kuei Hung Lai, Bo Rong Peng, Yu Ming Hsu, Mohamed El-Shazly, Ying Chi Du, Mei Chin Lu, Jui Hsin Su, Yi Chang Liu

研究成果: 雜誌貢獻文章同行評審

摘要

Manoalide was studied as a potential anti-inflammatory agent for the last forty years and more than 200 publications and 180 patents were reported on this compound. However, the configurations at positions 24 and 25 and configuration-dependent bioactivity were not yet studied. In the current report, ten manoalide-like sesterterpenoids were isolated from Luffariella sp. (1–10). These stereoisomers were identified and separated for the first time since 1980 and their configurations at positions 24 and 25 were determined by analyzing their spectroscopic spectra. The configuration-dependent anti-proliferative activity of manoalide derivatives was examined by evaluating their effect on four leukemic cancer cell lines (Molt 4, K562, Sup-T1, and U937). The 24R,25S-isomers exhibited the most potent activity (IC50 0.50–7.67 μM). The anti-proliferative mechanism of action of 24R,25S-manoalide (7) was further studied on Molt 4 cells. Compound 7 exhibited apoptotic activity on Molt 4 cells through the disruption of mitochondrial membrane potential (MMP) and the generation of intracellular reactive oxygen species (ROS). It also inhibited the activity of human topoisomerase I and II. The apoptotic-inducing effect of 7 was further supported by the in vivo experiment by suppressing the volume of xenograft tumor growth (66.11%) compared with the control.
原文英語
文章編號105150
期刊Bioorganic Chemistry
114
DOIs
出版狀態已發佈 - 九月 2021

ASJC Scopus subject areas

  • 生物化學
  • 分子生物學
  • 藥物發現
  • 有機化學

指紋

深入研究「The Configuration-Dependent Anti-Leukemic Effect of Manoalide Stereoisomers: Reignite Research Interest in these Sponge-Derived Sesterterpenoids」主題。共同形成了獨特的指紋。

引用此