Synthesis and Biological Evaluation of Novel Bromophenol Derivatives as Carbonic Anhydrase Inhibitors

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Akbaba Y., BALAYDIN H. T., MENZEK A., GÖKSU S., ŞAHİN E., EKİNCİ D.

ARCHIV DER PHARMAZIE, vol.346, no.6, pp.447-454, 2013 (SCI-Expanded)

• Publication Type: Article / Article
• Volume: 346 Issue: 6
• Publication Date: 2013
• Doi Number: 10.1002/ardp.201300054
• Journal Name: ARCHIV DER PHARMAZIE
• Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Index Chemicus (IC)
• Page Numbers: pp.447-454
• Keywords: Bromination, Bromophenols, Carbonic anhydrase inhibitors, Natural products, IN-VITRO, ANTIMICROBIAL ACTIVITIES, GLUTATHIONE-REDUCTASE, CONCISE SYNTHESIS, ISOZYMES I, ANTIOXIDANT, PHENOLS
• Ondokuz Mayıs University Affiliated: Yes

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-2methylphenyl)( 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 K-I values were calculated. The K-I values of the novel compounds were measured in the range of 13.7-32.7 mu M for the hCA I isozyme and 0.65-1.26 mu M 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 (K-I: 36.2 mu M), but rather less activity against hCA II.