Tyrosine kinase inhibitory activity of dehydroabietylamine derivatives tested by homogeneous time-resolved fluorescence based high throughput screening model / 中国天然药物

Protein tyrosine kinases (PTKs) are attractive targets in searching for therapeutic agents against many diseases. In this study, a series of dehydroabietylamine derivatives were first determined to show PTK inhibitory activity using a high-throughput screening (HTS) method based on homogeneous time-resolved fluorescence (HTRF) technology. The structure-activity relationships of the dehydroabietylamine derivatives were established, and it was found that the compounds with a nitrogen-containing side chain had better inhibitory activity. Further studies showed that the compounds substituted with halogen in the phenyl ring resulted in higher inhibitory activity on the epidermal growth factor receptor (EGFR), and can be a guide to modify the structure of dehydroabietylamine derivatives. Dehydroabietylamine derivatives might be a new class of multi-targeted and effective PTK inhibitors with structure modifications.

Inhibition of glucometabolism by a novel dehydroabielylamine derivative,DHAA-urea,in human hepatoma HepG2 cells / 中国药科大学学报

The effects of DHAA-urea,a novel dehydroabietylamine(DHAA) derivatives,on cell viability and glucose metabolism,in hypoxia and normoxia human hepatoma HepG2 cells were investigated.Hypoxia cells were achieved using DMEM containing high concentration of glucose without serum and pre-incubating of CoCl_2 (final concentration 150 μmol/L) for 24 h.The antiproliferation effect of DHAA-urea was measured by colorimetric MTT assay.The cellular ATP concentration,the lactate dehydrogenase(LDH) and glucose-6-phosphate dehydro genase (G6PD) activity were detected by their kits.It was shown that DHAA-urea markedly inhibited cell viability,cellular ATP level,LDH and G6PD activity in either aerobic or anaerobic circumstance in a dose-and time dependent manner.This suggested that DHAA-urea possibly inhibited HepG2 cells growth via the inhibition of glucolysis and glucolysis-dependent ATP depletion.DHAA-urea could be a promising candidate in the development of a novel class of agents used for human hepatocellular carcinoma.