Atıf İçin Kopyala
BOZTAS M., ÇETİNKAYA Y., TOPAL M., GÜLÇİN İ., MENZEK A., ŞAHİN E., ...Daha Fazla
JOURNAL OF MEDICINAL CHEMISTRY, cilt.58, sa.2, ss.640-650, 2015 (SCI-Expanded)
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Yayın Türü:
Makale / Tam Makale
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Cilt numarası:
58
Sayı:
2
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Basım Tarihi:
2015
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Doi Numarası:
10.1021/jm501573b
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Dergi Adı:
JOURNAL OF MEDICINAL CHEMISTRY
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Derginin Tarandığı İndeksler:
Science Citation Index Expanded (SCI-EXPANDED), Scopus
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Sayfa Sayıları:
ss.640-650
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Atatürk Üniversitesi Adresli:
Evet
Özet
Cyclopropylcarboxylic acids and esters and cyclopropylmethanols incorporating bromophenol moieties were investigated as inhibitors of the carbonic anhydrase enzyme (CA; EC 4.2.1.1). The cis- and trans-esters 5 and 6 were obtained from the reaction of 4-allyl-1,2-dimethoxybenzene (4) with ethyl diazoacetate, which after bromination with Br-2 gave two isomeric monobromides (11 and 15), four isomeric dibromides (12, 13, 16, and 17), and two isomeric tribromides (14 and 18). The carboxylic acids 7, 8, and 1926 were thereafter obtained by hydrolysis of the synthesized esters. All these bromophenol derivatives were tested against human (h) CA isoenzymes I and II (cytosolic, ubiquitous isoforms) and hCA IX and XII (transmembrane, tumor-associated enzymes). All tested bromophenols exhibited excellent inhibitory effects, in the low nanomolar range, with K-i values in the range of 0.5459 nM against hCA I and in the range of 0.97-12.14 nM against hCA II, whereas they were low micromolar inhibitors against hCA IX and XII. The best hCA I inhibition was observed in new bromophenol derivative 20 (Ki = 0.54 nM). On the other hand, new bromophenol derivative 12 showed a powerful inhibition effect against hCA II (K-i = 0.97 nM).