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Synthesis and Biological Evaluation of Novel Bromophenol Derivatives as Carbonic Anhydrase Inhibitors
Authors:Yusuf Akbaba  Halis Türker Balaydın  Abdullah Menzek  Süleyman Göksu  Ertan Şahin  Deniz Ekinci
Affiliation:1. Faculty of Science, Department of Chemistry, Atatürk University, Erzurum, Turkey;2. Faculty of Education, Science Educating Department, Artvin Coruh University, Artvin, Turkey;3. Faculty of Agriculture, Department of Agricultural Biotechnology, Ondokuz May?s University, Samsun, Turkey
Abstract:Here, we provide an alternative synthesis of the natural bromophenol 3,4‐dibromo‐5‐(2,3‐dibromo‐4,5‐dihydroxybenzyl)‐6‐(ethoxymethyl)benzene‐1,2‐diol ( 3 ) and the first synthesis of (4,5‐dihydroxy‐2‐methylphenyl)(3,4‐dihydroxyphenyl)methanone ( 18 ) and its brominated derivatives 19 – 21 . The compounds were characterized and tested against the two most studied members of the pH regulatory enzyme family, carbonic anhydrase (CA). The inhibitory potencies of the novel compounds and two natural bromophenols 2 , 3 were analyzed at the human isoforms hCA I and hCA II as targets and the KI values were calculated. The KI values of the novel compounds were measured in the range of 13.7–32.7 µM for the hCA I isozyme and 0.65–1.26 µM for the hCA II isozyme. The structurally related compound 14 was also tested in order to understand the structure–activity relationship, and the clinically used sulfonamide acetazolamide (AZA) was tested for comparison reasons. All of the compounds exhibited competitive inhibition with 4‐nitrophenylacetate as substrate. The compounds showed strong inhibitory activity against hCA I, being more effective as compared to the clinically used AZA (KI: 36.2 µM), but rather less activity against hCA II.
Keywords:Bromination  Bromophenols  Carbonic anhydrase inhibitors  Natural products
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