Synthesis and biological evaluation of novel bromophenol derivatives as carbonic anhydrase inhibitors
Yükleniyor...
Dosyalar
Tarih
2013
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Wiley-V C H Verlag Gmbh
Erişim Hakkı
info:eu-repo/semantics/closedAccess
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.
Açıklama
Anahtar Kelimeler
Bromination, Bromophenols, Carbonic anhydrase inhibitors, Natural products
Kaynak
Archiv der Pharmazie
WoS Q Değeri
N/A
Scopus Q Değeri
Q1
Cilt
346
Sayı
6
Künye
Akbaba, Y., Balaydın, H. T., Menzek, A., Göksu, S., Şahin, E., & Ekinci, D. (2013). Synthesis and biological evaluation of novel bromophenol derivatives as carbonic anhydrase inhibitors. Archiv der Pharmazie, 346(6), 447-454.
