期刊
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
卷 29, 期 4, 页码 469-475出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/14756366.2013.804072
关键词
Carbonic anhydrase; grayanotoxin III; molecular docking
资金
- FP7 EU project (Metoxia)
- [TAGEM-11/AR-GE/15.2011]
Grayanotoxin III (GTX3) was investigated for inhibition of all catalytically active mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms, i.e. CA I to CA XIV. It showed micromolar inhibition (K(I)s of 8.01 and 6.13 mu M) for cytosolic isoforms CA I and II, respectively. GTX3 showed a submicromolar inhibition (K(I)s in the range of 0.51-2.15 mu M) for the remaining cytosolic (CA III, VII and XIII), membrane-associated/transmembrane (CA IV, IX, XII and XIV), mitochondrial (CA VA and CA VB) and secreted (CA VI) isoforms. This inhibition profile is very different from that of the sulfonamide CA inhibitors (CAIs), which possess different clinical applications. A molecular docking study for GTX3 within the active sites of CA I and II assisted to the understanding of molecular mechanism of the ligand. The interesting inhibition profile, coupled with various possibilities of interacting with the enzyme active site make this family of natural compounds attractive leads for designing novel chemotypes acting as CAIs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据