ABSTRACT
Traditional Chinese medicine treatment of diseases has been recognized, but the material basis and mechanisms are not clear. In this study, target prediction of the antigastric cancer (GC) effect of Guiqi Baizhu (GQBZP) and the analysis of potential key compounds, key targets, and key pathways for the therapeutic effects against GC were carried out based on the method of network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment. There were 33 proteins shared between GQBZP and GC, and 131 compounds of GQBZP had a high correlation with these proteins, indicating that the PI3K-AKT signaling pathway might play a key role in GC. From these studies, we selected human epidermal growth factor receptor 2 (HER2) and programmed cell death 1-ligand 1 (PD-L1) for docking; the results showed that 385 and 189 compounds had high docking scores with HER2 and PD-L1, respectively. Six compounds were selected for microscale thermophoresis (MST). Daidzein/quercetin and isorhamnetin/formononetin had the highest binding affinity for HER2 and PD-L1, with Kd values of 3.7 µmol/L and 490, 667, and 355 nmol/L, respectively. Molecular dynamics simulation studies based on the docking complex structures as the initial conformation yielded the binding free energy between daidzein/quercetin with HER2 and isorhamnetin/formononetin with PD-L1, calculated by molecular mechanics Poisson-Boltzmann surface area, of -26.55, -14.18, -19.41, and -11.86 kcal/mol, respectively, and were consistent with the MST results. In vitro experiments showed that quercetin, daidzein, and isorhamnetin had potential antiproliferative effects in MKN-45 cells. Enzyme activity assays showed that quercetin could inhibit the activity of HER2 with an IC50 of 570.07 nmol/L. Our study provides a systematic investigation to explain the material basis and molecular mechanism of traditional Chinese medicine in treating diseases.
Subject(s)
B7-H1 Antigen/metabolism , Drugs, Chinese Herbal/metabolism , Neoplasm Proteins/metabolism , Receptor, ErbB-2/metabolism , Stomach Neoplasms/metabolism , B7-H1 Antigen/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Drugs, Chinese Herbal/therapeutic use , Humans , Isoflavones/metabolism , Isoflavones/pharmacology , Molecular Docking Simulation/methods , Neoplasm Proteins/chemistry , Phosphatidylinositol 3-Kinases/metabolism , Protein Structure, Quaternary , Protein Structure, Tertiary , Proto-Oncogene Proteins c-akt/metabolism , Quercetin/analogs & derivatives , Quercetin/metabolism , Quercetin/pharmacology , Receptor, ErbB-2/antagonists & inhibitors , Receptor, ErbB-2/chemistry , Signal Transduction , Stomach Neoplasms/drug therapyABSTRACT
Four novel lactams, colletotrilactam A-D (1-4), along with six known compounds (5-10) were isolated from the culture broth of Colletotrichum gloeosporioides GT-7, a fungal endophyte of Uncaria rhynchophylla. The structures of these compounds were elucidated by comprehensive NMR spectroscopy. Isolates were tested for monoamine oxidase (MAO) inhibitory activity and compound 9 showed potent MAO inhibitory activity with IC50 value of 8.93±0.34µg/mL, when the IC50 value of iproniazid as a standard was 1.80±0.5µg/mL.
Subject(s)
Colletotrichum/chemistry , Lactams/chemistry , Monoamine Oxidase Inhibitors/chemistry , Uncaria/microbiology , Endophytes/chemistry , Lactams/isolation & purification , Molecular Structure , Monoamine Oxidase/metabolism , Monoamine Oxidase Inhibitors/isolation & purificationABSTRACT
Wortmannolol (1), a new furanosteroid, along with five known compounds, wortmannolone (2), ergosterol (3), p-hydroxyphenyl ethanol (4), trans-6-dodecene (5), (2Z, 4E) -5-(8-hydroxy-1,5-dimethyl-3-oxo-6-oxabicyclo [3.2.1] octan-8-yl) -3-methylpenta-2,4-dienoic acid (6) were isolated from a fungal endophyte Talaromyces sp. lgt-4. Their structures were elucidated by IR, MS, 1D and 2D NMR spectra. Compound 1 show weak monoamine oxidase inhibitory activity.
Subject(s)
Talaromyces/chemistry , Alkanes/isolation & purification , Alkanes/pharmacology , Drug Evaluation, Preclinical/methods , Endophytes/chemistry , Ergosterol/isolation & purification , Ergosterol/pharmacology , Magnetic Resonance Spectroscopy , Molecular Structure , Monoamine Oxidase Inhibitors/chemistry , Monoamine Oxidase Inhibitors/pharmacology , Phenylethyl Alcohol/analogs & derivatives , Phenylethyl Alcohol/isolation & purification , Phenylethyl Alcohol/pharmacology , Sterols/isolation & purification , Sterols/pharmacology , Tripterygium/microbiologyABSTRACT
Nine new monoterpenoid indole alkaloids, ervatamines A-I (1-9), and five known ones (10-14), were isolated from Ervatamia hainanensis. The new structures were elucidated by extensive spectroscopic analysis and comparison to known compounds. Their absolute configurations were determined by various methods including computational methods, X-ray diffraction analysis, and electronic circular dichroism spectroscopy, as well as chemical transformations. Ervatamine A (1) is a ring-C-contracted ibogan-type monoterpenoid indole alkaloid with an unusual 6/5/6/6/6 pentacyclic rearranged ring system. Ervatamines B-E (2-5) display a nitrogen-containing 9/6 ring system, which is rarely observed in nature. The epimeric ervatamines B (2) and C (3) possess a 22-nor-monoterpenoid indole alkaloid carbon skeleton, which was only found in deformylstemmadenine. Compounds 10 and 14 exhibited significant anti-inflammatory activities, with IC50 values of 25.5 and 41.5 µM, respectively, while the IC50 value of indomethacin as a positive control was found to be 42.6 µM. Additionally, compound 9 showed mild activity against 786-O and HL-60 cell lines.