Ozlem Akgul, Gioele Renzi, Andrea Angeli, Marta Ferraroni, Fabrizio Carta, Claudiu T. Supuran
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引用次数: 0
Abstract
A series of taurinamide-based amides 1–19 were investigated for their effects on human (h) carbonic anhydrase (CA; EC 4.2.1.1) isoforms I, II, VA, VII, IX, and XII, which are all relevant for biomedical applications. According to inhibition data, most of the derivatives displayed affinity and selectivity for the hCA I isoform over the other isoforms tested, and compounds 1, 2, 4, 8, and 9 emerged as potent nanomolar inhibitors of hCA I and hCA IX, exhibiting KI values in the range of 0.65–0.83 and 0.59–0.96 µM, respectively (asetazolamide KI = 0.25 for CA I and KI = 0.03 M for hCA IX). The X-ray structures of 15 and 18 in complex with hCA II provided detailed insights into the binding mode and molecular determinants. Substitution patterns were found to have a tuning effect on both affinity and selectivity toward specific isoforms, thus providing valuable insights for the design of new CA inhibitors.
期刊介绍:
Archiv der Pharmazie - Chemistry in Life Sciences is an international journal devoted to research and development in all fields of pharmaceutical and medicinal chemistry. Emphasis is put on papers combining synthetic organic chemistry, structural biology, molecular modelling, bioorganic chemistry, natural products chemistry, biochemistry or analytical methods with pharmaceutical or medicinal aspects such as biological activity. The focus of this journal is put on original research papers, but other scientifically valuable contributions (e.g. reviews, minireviews, highlights, symposia contributions, discussions, and essays) are also welcome.