ABSTRACT
Fifteen metabolites, including two flavonols (1-2), three lignans (3-5), and ten diterpenoids (6-15), were isolated from the leaves of Pinus yunnanensis. Among them, flavanonol (1) were identified as undescribed flavonol derivative with natural rarely B-ring fission lactone. Massive spectroscopic methods, the DP4+ probabilities and CD/ECD calculations were applied to establish the structure of component 1. Among these compounds, taxifolin (2) showed potent cytotoxicity, having IC50 values from 21.33 to 45.48â µg/mL, it also showed broad antibacterial activity against human pathogens with MIC values from 32 to 64â µg/mL.
Subject(s)
Anti-Bacterial Agents/chemistry , Pinus/chemistry , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Diterpenes/chemistry , Diterpenes/isolation & purification , Diterpenes/pharmacology , Flavonols/chemistry , Flavonols/isolation & purification , Flavonols/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Conformation , Pinus/metabolism , Plant Extracts/chemistry , Plant Leaves/chemistry , Plant Leaves/metabolismABSTRACT
Six new guaiane-type sesquiterpenes (1-6), and one monoterpenoid (7) along with five known analogues (8-12), were isolated from the leaves of Artemisia argyi Lévl et Vant. The new compounds were characterized by the basic analysis of the spectroscopic data (HRMS, 1D and 2D NMR), and the absolute configurations were determined by both calculated electronic circular dichroism and DP4 calculations. The inhibitory effects of 1-12 against human gastric adenocarcinoma (AGS) cells were investigated in vitro, among which 1-3 and 8 showed remarkable cytotoxic activity with IC50 values in the range of 6.69-10.25 µM. The results suggested that the variation in the inhibitory activities of the compounds are the result of different substitutions on C-8. In order to rationalize the binding interactions of active compounds with the active site of NF-кB, in silico study was conducted and the results were in complete agreement with the experimental data for cytotoxicity evaluation.
Subject(s)
Adenocarcinoma/pathology , NF-kappa B/antagonists & inhibitors , Sesquiterpenes, Guaiane/pharmacology , Stomach Neoplasms/pathology , Humans , Spectrum Analysis/methods , Tumor Cells, CulturedABSTRACT
Ohwia caudata (OC)-a traditional Chinese medicine (TCM)-has been reported to have large numbers of flavonoids, alkaloids, and triterpenoids. The previous studies on OC for treating Alzheimer's disease (AD) only focused on single targets and its mechanisms, while no report had shown about the synergistic mechanism of the constituents from OC related to their potential treatment on dementia in any database. This study aimed to predict the bioactive targets constituents and find potential compounds from OC with better oral bioavailability and blood-brain barrier permeability against AD, by using a system network level-based in silico approach. The results revealed that two new flavonoids, and another 26 compounds isolated from OC in our lab, were highly connected to AD-related signaling pathways and biological processes, which were confirmed by compound-target network, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, respectively. Predicted by the virtual screening and various network pharmacology methods, we found the multiple mechanisms of OC, which are effective for alleviating AD symptoms through multiple targets in a synergetic way.
