Several bacteria rely on the reductive sulphur assimilation pathway, absent in mammals, to synthesise cysteine. Reduction of virulence and decrease in antibiotic resistance have already been associated with mutations on the genes that codify cysteine biosynthetic enzymes. Therefore, inhibition of cysteine biosynthesis has emerged as a promising strategy to find new potential agents for the treatment of bacterial infection. Following our previous efforts to explore OASS inhibition and to expand and diversify our library, a scaffold hopping approach was carried out, with the aim of identifying a novel fragment for further development. This novel chemical tool, endowed with favourable pharmacological characteristics, was successfully developed, and a preliminary Structure–Activity Relationship investigation was carried out.

Discovery of novel fragments inhibiting O-acetylserine sulphhydrylase by combining scaffold hopping and ligand–based drug design / Magalhães, Joana; Franko, Nina; Annunziato, Giannamaria; Welch, Martin; Dolan, Stephen K.; Bruno, Agostino; Mozzarelli, Andrea; Armao, Stefano; Jirgensons, Aigars; Pieroni, Marco; Costantino, Gabriele; Campanini, Barbara. - In: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY. - ISSN 1475-6366. - 33:1(2018), pp. 1444-1452. [10.1080/14756366.2018.1512596]

Discovery of novel fragments inhibiting O-acetylserine sulphhydrylase by combining scaffold hopping and ligand–based drug design

Magalhães, Joana;Franko, Nina;Annunziato, Giannamaria;Bruno, Agostino;Mozzarelli, Andrea;Armao, Stefano;Pieroni, Marco
;
Costantino, Gabriele;Campanini, Barbara
2018

Abstract

Several bacteria rely on the reductive sulphur assimilation pathway, absent in mammals, to synthesise cysteine. Reduction of virulence and decrease in antibiotic resistance have already been associated with mutations on the genes that codify cysteine biosynthetic enzymes. Therefore, inhibition of cysteine biosynthesis has emerged as a promising strategy to find new potential agents for the treatment of bacterial infection. Following our previous efforts to explore OASS inhibition and to expand and diversify our library, a scaffold hopping approach was carried out, with the aim of identifying a novel fragment for further development. This novel chemical tool, endowed with favourable pharmacological characteristics, was successfully developed, and a preliminary Structure–Activity Relationship investigation was carried out.
Discovery of novel fragments inhibiting O-acetylserine sulphhydrylase by combining scaffold hopping and ligand–based drug design / Magalhães, Joana; Franko, Nina; Annunziato, Giannamaria; Welch, Martin; Dolan, Stephen K.; Bruno, Agostino; Mozzarelli, Andrea; Armao, Stefano; Jirgensons, Aigars; Pieroni, Marco; Costantino, Gabriele; Campanini, Barbara. - In: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY. - ISSN 1475-6366. - 33:1(2018), pp. 1444-1452. [10.1080/14756366.2018.1512596]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

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

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2850439
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 14
  • ???jsp.display-item.citation.isi??? 14
social impact