Structure–Activity Relationship of Halophenols as a New Class of Protein Tyrosine Kinase Inhibitors

Abstract

A series of new benzophenone and diphenylmethane halophenol derivatives were prepared. Their structures were established based on 1H NMR, 13C 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.

Protective Effect of 2,4′,5′-Trihydroxyl-5,2′-dibromo diphenylmethanone, a New Halophenol, against Hydrogen Peroxide-Induced EA.hy926 Cells Injury

“…Halophenols, isolated from halobios such as various marine algae, ascidians and sponges exhibit a wide spectrum of bioactivities including protein tyrosine phosphatase (PTP1B) inhibitory [10], antioxidative [11,12], antithrombotic [13], antimicrobial [14,15], anti-inflammatory [16], enzyme inhibitory [17], cytotoxic [18], appetite suppressant [19], and PTK inhibitory activities [20]. Recently, we synthesized a variety of halophenols including 2,4′,5′-trihydroxyl-5,2′-dibromo diphenylmethanone (TDD, Figure 1), which has strong antioxidative and cytoprotective activities [21,22,23]. However, the detailed mechanisms underscoring its actions are unclear.…”

Efficient Transfer Hydrodehalogenation of Halophenols Catalyzed by Pd Supported on Ceria

“…As such, they are often released to the environment where they can negatively impact several organisms, either through their immediate toxicity or by inducing long term reproductive effects and cancers. [1][2][3][4][5] Therefore, developing dehalogenation methods is critical from an environmental standpoint. A common approach for removing halogen atoms from organic compounds is catalytic hydrodehalogenation.…”

Non-Innocent Role of the Ceria Support in Pd-Catalyzed Halophenol Hydrodehalogenation

“…For example, halophenols are widely used as synthetic building blocks, pesticides, fungicides and wood preservers, and are also common pollutants. [15][16][17] While Pd/CeO2 catalyzes halogen removal from aromatics via hydrodehalogenation (HDH), [18][19][20][21][22][23][24] it is not clear how the presence of the hydroxyl group in halophenols affects this reactivity or if it can also induce an alternative dearomatization pathway as is the case with methoxyphenols. In this work, we explored the effect of hydroxyl on the Pd/CeO2 catalyzed HDH of halophenols.…”

“…Substituted phenolics are a common motif in a variety of chemical commodities. For example, halophenols are widely used as synthetic building blocks, pesticides, fungicides, and wood preservers and are also common pollutants. − Although Pd/CeO 2 catalyzes halogen removal from aromatics via hydrodehalogenation (HDH), − it is not clear how the presence of the hydroxyl group in halophenols affects this reactivity or if it can also induce an alternative dearomatization pathway as is the case with methoxyphenols.…”