The first synthesis of 4-phenylbutenone derivative bromophenols including natural products and their inhibition profiles for carbonic anhydrase, acetylcholinesterase and butyrylcholinesterase enzymes

Abstract

The first synthesis of (E)-4-(3-bromo-4,5-dihydroxyphenyl)but-3-en-2-one (1), (E)-4-(2-bromo-4,5-dihydroxyphenyl)but-3-en-2-one (2), and (E)-4-(2,3-dibromo-4,5-dihydroxyphenyl)but-3-en-2-one (3) was realized as natural bromophenols. Derivatives with mono OMe of 2 and 3 were obtained from the reactions of their derivatives with di OMe with AlCl3. These novel 4-phenylbutenone derivatives were effective inhibitors of the cytosolic carbonic anhydrase I and II isoenzymes (hCA I and II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with Ki values in the range of 158.07–404.16pM for hCA I, 107.63–237.40pM for hCA II, 14.81–33.99pM for AChE and 5.64–19.30pM for BChE. The inhibitory effects of the synthesized novel 4-phenylbutenone derivatives were compared to acetazolamide as a clinical hCA I and II isoenzymes inhibitor and tacrine as a clinical AChE and BChE enzymes inhibitor.