Structure-activity relationship of halophenols as a new class of protein tyrosine kinase inhibitors

• Published in: International journal of molecular sciences Vol. 12; no. 9; pp. 6104 - 6115
• Main Authors: Feng, Xiu E, Zhao, Wan Yi, Ban, Shu Rong, Zhao, Cheng Xiao, Li, Qing Shan, Lin, Wen Han
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.09.2011; Molecular Diversity Preservation International (MDPI)
• Subjects: Animals; Benzhydryl Compounds - chemistry; benzophenone; Benzophenones - chemistry; Cancer; diphenylmethane; Halogens - chemistry; halophenol; Kinases; Magnetic Resonance Spectroscopy; Male; Mice; Models, Chemical; Molecular Structure; Phenols - chemical synthesis; Phenols - chemistry; Phenols - pharmacology; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; protein tyrosine kinase; Protein-Tyrosine Kinases - antagonists & inhibitors; Proteins; Signal transduction; Structure-Activity Relationship; China; benzophenone; halophenol; diphenylmethane; protein tyrosine kinase; structure-activity relationship
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms12096104

A series of new benzophenone and diphenylmethane halophenol derivatives were prepared. Their structures were established based on (1)H NMR, (13)C NMR and HRMS data. All prepared compounds were screened for their in vitro protein tyrosine kinase (PTK) inhibitory activities. The effects of modification of the linker, functional groups and substituted positions at the phenyl ring on PTK inhibitory activity were investigated. Twelve halophenols showed significant PTK inhibitory activity. Among them, compounds 6c, 6d, 7d, 9d, 10d, 11d and 13d exhibited stronger activities than that of genistein, the positive reference compound. The results gave a relatively full and definite description of the structure-activity relationship and provided a foundation for further design and structure optimization of the halophenols.