ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Infection is a major group of diseases which caused significant mortality and morbidity worldwide. Traditional Chinese herbs have been used to treat infective diseases for thousands years. The numerous clinical practices in disease therapy make it a large chemical resource library for drug discovery. MATERIALS AND METHODS: In this study, we collected 1156 kinds of herbs and 22,172 traditional Chinese medicinal compounds (Tcmcs). The chemical informatics and network pharmacology were employed to analyze the anti-infective effects of herbs and Tcmcs. In order to evaluate the drug likeness of Tcmcs, the molecular descriptors of Tcmcs and FDA-approved drugs were calculated and the chemical space was constructed on the basis of principal component analysis in the eight descriptors. On purpose to estimate the effects of Tcmcs to the targets of FDA-approved anti-infective or anti-inflammatory drugs, the molecular docking was employed. After that, docking score weighted predictive models were used to predict the anti-infective or anti-inflammatory efficacy of herbs. RESULTS: The distribution of herbs in the phylogenetic tree showed that most herbs were distributed in family of Asteraceae, Fabaceae and Lamiaceae. Tcmcs were well coincide with drugs in chemical space, which indicated that most Tcmcs had good drug-likeness. The predictive models obtained good specificity and sensitivity with the AUC values above 0.8. At last, 389 kinds of herbs were obtained which were distributed in 100 families, by using the optimal cutoff values in ROC curves. These 389 herbs were widely used in China for treatment of infection and inflammation. CONCLUSION: Traditional Chinese herbs have a considerable number of drug-like natural products and predicted activities to the targets of approved drugs, which would give us an opportunity to use these herbs as a chemical resource library for drug discovery of anti-infective and anti-inflammatory.
Subject(s)
Anti-Infective Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Drugs, Chinese Herbal/pharmacology , Medicine, Chinese Traditional/methods , Anti-Infective Agents/isolation & purification , Anti-Inflammatory Agents/isolation & purification , Biological Products , China , Drug Discovery/methods , Drugs, Chinese Herbal/chemistry , Ethnopharmacology , Humans , Models, Theoretical , Molecular Docking Simulation , Plants, Medicinal/chemistry , Principal Component Analysis , Sensitivity and SpecificityABSTRACT
Five 4-arylcoumarins (1c-g) and twelve 3,4-dihydro-4-arylcoumarins (2a-l) were synthesized and tested for antioxidant activity, antitumor activity, toxicity and structure-activity relationships analysis. 4-Arylcoumarins and 3,4-dihydro-4-arylcoumarins that possess two hydroxyl groups in ortho position, such as 1d, 1f, 2a, 2f, 2g and 2h had stronger radical scavenging properties than that of vitamin C (Vit C) in ABTS(+) assay. Kinetic traces of scavenging ABTS(+) and DPPH radicals showed that all the reaction could reached endpoint in 1 min, which was similar with Vit C. 4-Arylcoumarins with 3'-hydroxyl-4'-methylphenyl structural show more efficient NO radical scavenging activity. Three compounds 2e, 1f and 2a, in particular had superior EC50 for NO scavenging than did Vit C. MTT assay indicated that one compound in particular had a potential antitumor effect, inhibiting proliferation of BGC-823 cells and almost completely killing them at a concentration 62.5 mg/L. With same concentration 100 µg/mL, hemolytic analysis in rabbit red blood cells showed that only two compounds had hemolytic activity with a little more than 5% hemolysis. Injection and oral toxicity tests on Galleria mellonella larvae showed that none of the tested 4-arylcoumarins significantly affected their appetite, viability and mortality.
