ABSTRACT
Gastric cancer is one of the common malignant tumors. It is reported that daphne-type diterpenes have inhibitory effects on gastric cancer cells, but the mechanism is still unknown. To explore the detailed mechanism of the anticancer effect of daphne-type diterpenes, we carried out an integrated network pharmacology prediction study and selected an effective component (yuanhuacine, YHC) for the following validation in silico and in vitro. The result showed that daphne-type diterpenes exerted an anti-tumor effect by targeting proto-oncogene tyrosine-protein kinase SRC as well as regulating the Ras/MAPK signaling pathway, which caused the apoptosis and mitochondrial damage in gastric cancer cells.
ABSTRACT
Four pairs of aryldihydronaphthalene-type lignanamide enantiomers were isolated from Solanum lyratum (Solanaceae). The enantiomeric separation was accomplished by chiral-phase HPLC, and five undescribed compounds were elucidated. Analysis by various spectroscopy and ECD calculations, the structures of undescribed compounds were illuminated. The neuroprotective effects of all compounds were evaluated using H2 O2 -induced human neuroblastoma SH-SY5Y cells and AchE inhibition activity. Among them, compound 4 a exhibited remarkable neuroprotective effects at high concentrations of 25 and 50â µmol/L comparable to Trolox. Compound 1 a showed the highest AchE inhibition with the IC50 value of 3.06±2.40â µmol/L. Molecular docking of the three active compounds was performed and the linkage between the compounds and the active site of AchE was elucidated.
Subject(s)
Neuroblastoma , Neuroprotective Agents , Solanum , Humans , Solanum/chemistry , Neuroprotective Agents/chemistry , Molecular Docking Simulation , Stereoisomerism , Molecular StructureABSTRACT
Guiding by LC-MS/MS analysis and the GNPS Molecular Networking, five undescribed daphnane diterpenoids, tanguticanines A-E, and eleven known analogues were discovered from the whole plants of Daphne tangutica Maxim. Their structures and absolute configurations were determined via extensive NMR spectroscopic analysis, ECD calculations, and X-ray diffraction crystallography. Tanguticanine E (5) exhibited promising cytotoxicity against the HepG2 cell line with an IC50 value of 9.93 ± 0.10 µM. Further flow cytometry experiment was performed to detect cell apoptosis, and the results indicated that cytotoxic diterpenoids (tanguticanines B, D and E, altadaphnan C, gniditrin, hirsein A and simplexin) exert their effects through induction of apoptosis.
Subject(s)
Antineoplastic Agents , Daphne , Diterpenes , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Chromatography, Liquid , Daphne/chemistry , Diterpenes/chemistry , Esters/pharmacology , Molecular Structure , Tandem Mass SpectrometryABSTRACT
A molecular networking-guided study on the Daphne genkwa Sieb. et Zucc led to the isolation of twelve daphnane-type diterpenoids including four undescribed compounds, yuanhuakines A-D. Their structures were elucidated by spectroscopic analyses, ECD calculations, and single-crystal X-ray diffraction analysis. All isolates were evaluated for their inhibitory activity against the A549, Hep3B, and MCF-7 cell lines. The majority of compounds inhibited A549 cells with IC50 values ranging from 7.77 to 20.56 µM, and their structure-activity relationship is preliminarily discussed. Five of these compounds were selected for further experiments, and they appear to inhibit A549 cell lines by inducing apoptosis.
