PDBsum entry 5e28

Lyase

PDB id: 5e28

Contents

Protein chain

257 a.a.

Ligands

BC5

GOL

Metals

_ZN

Waters ×343

References listed in PDB file

Key reference

• Title: 4-Arylbenzenesulfonamides as human carbonic anhydrase inhibitors (hcais): synthesis by pd nanocatalyst-Mediated suzuki-Miyaura reaction, Enzyme inhibition, And X-Ray crystallographic studies.
• Authors: B.Cornelio, M.Laronze-Cochard, M.Ceruso, M.Ferraroni, G.A.Rance, F.Carta, A.N.Khlobystov, A.Fontana, C.T.Supuran, J.Sapi.
• Ref.: J Med Chem, 2016, 59, 721-732. [DOI no: 10.1021/acs.jmedchem.5b01771]
• PubMed id: 26741028

Abstract

Benzenesulfonamides bearing various substituted (hetero)aryl rings in the para-position were prepared by palladium nanoparticle-catalyzed Suzuki-Miyaura cross-coupling reactions and evaluated as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors against isoforms hCA I, II, IX, and XII. Most of the prepared sulfonamides showed low inhibition against hCA I isoform, whereas the other cytosolic isoenzyme, hCA II, was strongly affected. The major part of these new derivatives acted as potent inhibitors of the tumor-associated isoform hCA XII. An opposite trend was observed for phenyl, naphthyl, and various heteroaryl substituted benzenesulfonamides which displayed subnanomolar hCA IX inhibition while poorly inhibiting the other tumor-associated isoform hCA XII. The inhibition potency and influence of the partially restricted aryl-aryl bond rotation on the activity/selectivity were rationalized by means of X-ray crystallography of the adducts of hCA II with several 4-arylbenzenesulfonamides.