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-dihy droxyphenyl) 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 158.07-404.16 pM for hCA I, 107.63-237.40 pM for hCA II, 14.81-33.99 pM for AChE and 5.64-19.30 pM 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. (C) 2017 Elsevier Inc. All rights reserved.