genistein and flavanone

A series of new flavanone derivatives of farrerol was synthesized by a convenient method. The in vitro anti-tumor activity of these compounds was evaluated against human Bel-7402, HL-60, BGC-823 and KB cell lines, the protein tyrosine kinase (PTK) inhibitor activity was also tested. Their cytoprotective activity was tested using hydrogen peroxide (H2O2)-induced injury in human umbilical vein endothelial cells. Their in vitro anti-atherosclerosis activity was tested on vascular smooth muscle cells by the MTT method using tetrandrine as a positive contrast drug. The structures of all compounds synthesized were confirmed by 1H, 13C NMR and ESI-MS. Most of the compounds exhibited good pharmacological activity and the preliminary structure-activity relationships were described.

Topics: Antineoplastic Agents; Atherosclerosis; Cell Line; Cell Line, Tumor; Cell Proliferation; Cytoprotection; Endothelial Cells; Flavanones; Humans; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neoplasms; Protein-Tyrosine Kinases; Structure-Activity Relationship

Random Forest screening of the phytochemical constituents of 240 herbs used in traditional Chinese medicine identified a number of compounds as potential inhibitors of the human aromatase enzyme (CYP19). Molecular modelling/docking studies indicated that three of these compounds (myricetin, liquiritigenin and gossypetin) would be likely to form stable complexes with the enzyme. The results of the virtual screening studies were subsequently confirmed experimentally, by in vitro (fluorimetric) assay of the compounds' inhibitory activity. The IC-50s for the flavones, myricetin and gossypetin were determined as 10 and 11 microM, respectively, whilst the flavanone, liquiritigenin, gave an IC-50 of 0.34 microM--showing about a 10-fold increase in potency, therefore, over the first generation aromatase inhibitor, aminoglutethimide.

Topics: Algorithms; Aminoglutethimide; Aromatase Inhibitors; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Flavanones; Flavonoids; Fluorometry; Humans; Inhibitory Concentration 50; Models, Molecular; Structure-Activity Relationship