Phenylspirodrimane with Moderate Reversal Effect of Multidrug Resistance Isolated from the Deep-Sea Fungus Stachybotrys sp. 3A00409.
Xinhua MaMin WuZhenwei ChenFan CaoTianhua ZhongZhu-Hua LuoZongze ShaoYonghong ZhangLimin ChenZhiqiang ZhangPublished in: Molecules (Basel, Switzerland) (2024)
Two new phenylspirodrimanes, stachybotrins K and L ( 1 and 2 ), together with eight known analogues ( 3 - 10 ), were isolated from deep-sea-derived Stachybotrys sp. MCCC 3A00409. Their structures were determined by extensive NMR data and mass spectroscopic analysis. Absolute configurations of new compounds were determined through a comparison of their circular dichroism (CD) spectra with other reported compounds. The possible reversal effects of all compounds were assayed in the resistant cancer cell lines. Stachybotrysin B ( 8 ) can reverse multidrug resistance (MDR) in ABCB1-overexpression cells (KBv200, Hela/VCR) at the non-cytotoxic concentration. Doxorubicin accumulation assay and molecular-docking analysis reveal that the mechanism of its reversal MDR effect may be related to the increase in the intracellular concentration of substrate anticancer drugs.
Keyphrases
- molecular docking
- molecular dynamics simulations
- multidrug resistant
- induced apoptosis
- cell cycle arrest
- magnetic resonance
- drug delivery
- squamous cell carcinoma
- gene expression
- transcription factor
- machine learning
- signaling pathway
- high intensity
- dna methylation
- genome wide
- density functional theory
- deep learning
- data analysis
- childhood cancer