Dipartimento di Scienze del Farmaco, Università di Sassari, Via Muroni 23/A, 07100 Sassari, Italy.
Bioorg Med Chem Lett. 2011 Apr 15;21(8):2515-20. doi: 10.1016/j.bmcl.2011.02.059. Epub 2011 Feb 17.
Combinated ligand- and pharmacophore-based virtual screening approaches were used to discover novel potential pharmacophores acting as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors (CAIs). A free database of commercially available compounds was screened through drug-like filters using a four-point pharmacophore, and followed by docking calculation within the active site of an X-ray structure of isoform CA II. One compound, bearing a trifluoro-dihydroxy-propanone moiety, showed an interesting, selective inhibitory activity in low micromolar range against this isoform versus CA I. The chemical originality of this new pharmacophore can represent an important bioisosteric alternative to the sulfonamido-based functionalities, thus leading to the development of a new class of CAIs.
联合配体和基于药效团的虚拟筛选方法被用于发现新型潜在的药效团，作为碳酸酐酶（CA，EC 4.2.1.1）抑制剂（CAIs）。通过使用四点药效团对商业上可用的化合物进行自由数据库筛选，然后在 X 射线结构的活性部位进行对接计算。一个带有三氟二羟基丙酮部分的化合物在低微摩尔范围内对这种同工酶相对于 CA I 表现出有趣的选择性抑制活性。这种新药效团的化学创新性可以代表基于磺酰胺的功能的重要生物等排体替代物，从而导致新型 CAIs 的开发。
