A series of benzene sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitors which incorporate lipophilic 4-alkoxy- and 4-aryloxy moieties, together with several derivatives of ethoxzolamide and sulfanilamide are reported. These derivatives were investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) of which multiple isoforms are known, and some appear to be involved in pain. These sulfonamides showed modest inhibition against the cytosolic isoform CA I, but were generally effective, low nanomolar CA II, VII, IX and XII inhibitors. X-ray crystallographic data for the adduct of several such sulfonamides with CA II allowed us to rationalize the good inhibition data. In a mice model of neuropathic pain induced by oxaliplatin, one of the strong CA II/VII inhibitors reported here induced a long lasting pain relieving effect, a fact never observed earlier. This is the first report of rationally designed sulfonamide CA inhibitors with pain effective modulating effects.

A class of sulfonamide carbonic anhydrase inhibitors with neuropathic pain modulating effects / Carta, Fabrizio; Di Cesare Mannelli, Lorenzo; Pinard, Melissa; Ghelardini, Carla; Scozzafava, Andrea; Mckenna, Robert; Supuran, Claudiu T.. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - STAMPA. - 23:(2015), pp. 1828-1840. [10.1016/j.bmc.2015.02.027]

A class of sulfonamide carbonic anhydrase inhibitors with neuropathic pain modulating effects

CARTA, FABRIZIO;DI CESARE MANNELLI, LORENZO;GHELARDINI, CARLA;SCOZZAFAVA, ANDREA;SUPURAN, CLAUDIU TRANDAFIR
2015

Abstract

A series of benzene sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitors which incorporate lipophilic 4-alkoxy- and 4-aryloxy moieties, together with several derivatives of ethoxzolamide and sulfanilamide are reported. These derivatives were investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) of which multiple isoforms are known, and some appear to be involved in pain. These sulfonamides showed modest inhibition against the cytosolic isoform CA I, but were generally effective, low nanomolar CA II, VII, IX and XII inhibitors. X-ray crystallographic data for the adduct of several such sulfonamides with CA II allowed us to rationalize the good inhibition data. In a mice model of neuropathic pain induced by oxaliplatin, one of the strong CA II/VII inhibitors reported here induced a long lasting pain relieving effect, a fact never observed earlier. This is the first report of rationally designed sulfonamide CA inhibitors with pain effective modulating effects.
2015
23
1828
1840
Carta, Fabrizio; Di Cesare Mannelli, Lorenzo; Pinard, Melissa; Ghelardini, Carla; Scozzafava, Andrea; Mckenna, Robert; Supuran, Claudiu T.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1008895
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 126
  • ???jsp.display-item.citation.isi??? 122
social impact