Virtual screening-driven identification of human carbonic anhydrase inhibitors incorporating an original, new pharmacophore.

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Pala N, Dallocchio R, Dessi A, Brancale A, Carta F, Ihm S, Maresca A, Sechi M, Supuran CT

Virtual screening-driven identification of human carbonic anhydrase inhibitors incorporating an original, new pharmacophore.

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2515-20. doi: 10.1016/j.bmcl.2011.02.059. Epub 2011 Feb 17.

PubMed ID

21420862 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Acetazolamide	Carbonic anhydrase 1	Ki (nM)	900	N/A	N/A	Details
Acetazolamide	Carbonic anhydrase 2	Ki (nM)	12	N/A	N/A	Details