Inhibition of carbohydrate processing enzymes is a topic of great interest, as these enzymes are involved in a plethora of key biochemical events, such as digestion, lysosomal catabolism of glycoconjugates and post-translational glycoprotein processing. Among the most potent inhibitors of such enzymes, iminosugars have emerged as versatile tools for medicinal chemists, especially those in quest for new therapeutic agents. Supply of iminosugars from natural sources or by chemical synthesis has provided excellent targets for medical intervention, ranging from antidiabetics and antivirals to inhibitors of genetic disorders. Although a huge body of literature has been reported around iminosugars, most data have focused on D-series iminosugars, whereas relatively little attention has been devoted to the corresponding L-enantiomers, due to their supposed lack of biological activity profile, as well as their scarce availability from natural sources. Notwithstanding, recent insights into the molecular details of enzyme-inhibitor interactions have led to a reassessment of L-iminosugars for pharmaceutical purposes. On one hand, they have been used as tools for intensive SAR (structure-activity-relationship) studies, in order to gain new information on the enzymatic inhibition mechanisms. Likewise, early reports on biological activity of Liminosugars have led to reconsider their therapeutic skills. This review focuses on the most significant discoveries regarding medicinal chemistry of L-iminosugars. The important role L-iminosugars play in unravelling the inhibition mechanisms of specific enzymes is herein recognized; moreover, the high potential of this class of inhibitors as novel drug candidates is under discussion.

Glycomimetics at the Mirror: Medicinal Chemistry of L-Iminosugars / D'Alonzo, Daniele; Guaragna, Annalisa; Palumbo, Giovanni. - In: CURRENT MEDICINAL CHEMISTRY. - ISSN 0929-8673. - STAMPA. - 16:4(2009), pp. 473-502. [10.2174/092986709787315540]

Glycomimetics at the Mirror: Medicinal Chemistry of L-Iminosugars

D'ALONZO, DANIELE;GUARAGNA, ANNALISA;PALUMBO, GIOVANNI
2009

Abstract

Inhibition of carbohydrate processing enzymes is a topic of great interest, as these enzymes are involved in a plethora of key biochemical events, such as digestion, lysosomal catabolism of glycoconjugates and post-translational glycoprotein processing. Among the most potent inhibitors of such enzymes, iminosugars have emerged as versatile tools for medicinal chemists, especially those in quest for new therapeutic agents. Supply of iminosugars from natural sources or by chemical synthesis has provided excellent targets for medical intervention, ranging from antidiabetics and antivirals to inhibitors of genetic disorders. Although a huge body of literature has been reported around iminosugars, most data have focused on D-series iminosugars, whereas relatively little attention has been devoted to the corresponding L-enantiomers, due to their supposed lack of biological activity profile, as well as their scarce availability from natural sources. Notwithstanding, recent insights into the molecular details of enzyme-inhibitor interactions have led to a reassessment of L-iminosugars for pharmaceutical purposes. On one hand, they have been used as tools for intensive SAR (structure-activity-relationship) studies, in order to gain new information on the enzymatic inhibition mechanisms. Likewise, early reports on biological activity of Liminosugars have led to reconsider their therapeutic skills. This review focuses on the most significant discoveries regarding medicinal chemistry of L-iminosugars. The important role L-iminosugars play in unravelling the inhibition mechanisms of specific enzymes is herein recognized; moreover, the high potential of this class of inhibitors as novel drug candidates is under discussion.
2009
Glycomimetics at the Mirror: Medicinal Chemistry of L-Iminosugars / D'Alonzo, Daniele; Guaragna, Annalisa; Palumbo, Giovanni. - In: CURRENT MEDICINAL CHEMISTRY. - ISSN 0929-8673. - STAMPA. - 16:4(2009), pp. 473-502. [10.2174/092986709787315540]
File in questo prodotto:
File Dimensione Formato  
2009_CurrMedChem_L_Iminosugars.pdf

non disponibili

Tipologia: Documento in Post-print
Licenza: Accesso privato/ristretto
Dimensione 1.09 MB
Formato Adobe PDF
1.09 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

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/11588/346252
Citazioni
  • ???jsp.display-item.citation.pmc??? 13
  • Scopus 91
  • ???jsp.display-item.citation.isi??? 85
social impact