Design, synthesis and X-ray crystallography of selenides bearing benzenesulfonamide moiety with neuropathic pain modulating effects.

Basic Information

ID: ALA4152274

Journal: Eur J Med Chem

Title: Design, synthesis and X-ray crystallography of selenides bearing benzenesulfonamide moiety with neuropathic pain modulating effects.

Authors: Angeli A, di Cesare Mannelli L, Lucarini E, Peat TS, Ghelardini C, Supuran CT.

Abstract: A series of selenides bearing benzensulfonamide were investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Potent inhibitory action, in the low nanomolar range, was detected against isoforms hCA II and VII, which are known to be involved in neuropathic pain modulation. These selenides showed on the other hand moderate inhibition against the cytosolic isoforms hCA I and transmembrane hCA IX. X-ray crystallographic data of two derivatives bound to hCA II allowed us to rationalize the excellent inhibitory data. In a mice model of neuropathic pain induced by oxaliplatin, some of the strong CA II/VII inhibitors induced a long lasting pain relieving effect.

CiteXplore: 29803994

DOI: 10.1016/j.ejmech.2018.05.026

Patent ID: