N-Arylsulfonyl-based MMPs inhibitors (MMPIs) are among the most prominent inhibitors possessing nanomolar affinity. However, their poor bioavailability remains critical for the drug development of this family of molecules. The structural analysis of the complex of NNGH (the most representative member of the family) with MMP-12 provided us with the basis to effectively design simple NNGH analogues with enhanced solubility in water. Following this approach, the sec-butyl residue, not directly involved in the binding with MMP, has been replaced with hydrophilic residues thus yielding new potent inhibitors soluble in water.

Structure-Based Approach to Nanomolar, Water Soluble Matrix Metalloproteinases Inhibitors (MMPIs) / E.Attolino; V.Calderone; E.Dragoni; M.Fragai; B.Richichi; C.Luchinat; C.Nativi. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - STAMPA. - 45:(2010), pp. 5919-5925. [10.1016/j.ejmech.2010.09.057]

Structure-Based Approach to Nanomolar, Water Soluble Matrix Metalloproteinases Inhibitors (MMPIs)

CALDERONE, VITO;DRAGONI, ELISA;FRAGAI, MARCO;RICHICHI, BARBARA;LUCHINAT, CLAUDIO;NATIVI, CRISTINA
2010

Abstract

N-Arylsulfonyl-based MMPs inhibitors (MMPIs) are among the most prominent inhibitors possessing nanomolar affinity. However, their poor bioavailability remains critical for the drug development of this family of molecules. The structural analysis of the complex of NNGH (the most representative member of the family) with MMP-12 provided us with the basis to effectively design simple NNGH analogues with enhanced solubility in water. Following this approach, the sec-butyl residue, not directly involved in the binding with MMP, has been replaced with hydrophilic residues thus yielding new potent inhibitors soluble in water.
2010
45
5919
5925
E.Attolino; V.Calderone; E.Dragoni; M.Fragai; B.Richichi; C.Luchinat; C.Nativi
File in questo prodotto:
File Dimensione Formato  
2010_European_J_Med_CheM_45_5919-5945.pdf

Accesso chiuso

Tipologia: Versione finale referata (Postprint, Accepted manuscript)
Licenza: Tutti i diritti riservati
Dimensione 467.62 kB
Formato Adobe PDF
467.62 kB Adobe PDF   Richiedi una copia

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/2158/395434
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 29
  • ???jsp.display-item.citation.isi??? 28
social impact