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

AKBABA Y., Balaydin H. T., MENZEK A., GÖKSU S., ŞAHİN E., Ekinci D.

ARCHIV DER PHARMAZIE, cilt.346, sa.6, ss.447-454, 2013 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 346 Sayı: 6
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1002/ardp.201300054
  • Dergi Adı: ARCHIV DER PHARMAZIE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.447-454
  • Anahtar Kelimeler: Bromination, Bromophenols, Carbonic anhydrase inhibitors, Natural products, IN-VITRO, ANTIMICROBIAL ACTIVITIES, GLUTATHIONE-REDUCTASE, CONCISE SYNTHESIS, ISOZYMES I, ANTIOXIDANT, PHENOLS
  • Atatürk Üniversitesi Adresli: Evet

Özet

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.