title: Tyrosine kinase inhibitory activity of dehydroabietylamine derivatives tested by homogeneous time-resolved fluorescence based high throughput screening model.
abstract: 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.
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Tao-Tao
authors.initials: TT
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China. Electronic address: heling92@hotmail.com.
authors.forename: Ling
authors.initials: L
authors.lastname: He
authors.affiliation: National Drug Screening Laboratory, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.affiliation: National Drug Screening Laboratory, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Lu-Yong
authors.initials: LY
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Chongqing Red Cross Hospital, Chongqing 400020, China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: He
authors.affiliation: Institute of Chemical Industry of Forest Products, Chinese Academy of Forestry, Nanjing 210042, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Rao
mesh_terms: D004353:Drug Evaluation, Preclinical; D005453:Fluorescence; D057166:High-Throughput Screening Assays; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases
keywords: Dehydroabietylamine derivatives; High throughput screening; Homogeneous time-resolved fluorescence; Protein tyrosine kinases