Drawing inspiration from the structural features of some natural polyphenols, the synthesis of two different model compounds as potential inhibitors of HIV integrase (IN) has been described. The former was characterised by a diketo acid (DKA) bioisostere, such as a β-hydroxycarbonyl moiety, between two fragments containing aromatic groups, while in the latter an epoxide linked two polyoxygenated aromatic residues. The moieties present in the structures are thought to function by chelating divalent metal ions on the enzyme catalytic site. Overall, 10 compounds were prepared and some of that submitted to molecular modelling studies (to investigate their interactions with the active site of IN), to metal titration studies (to detect their chelating capability) and to biological assays.

Righi, G., Pelagalli, R., Isoni, V., Tirotta, I., Marini, M., Palagri, M., et al. (2018). Synthesis of potential HIV integrase inhibitors inspired by natural polyphenol structures. NATURAL PRODUCT RESEARCH, 32(16), 1893-1901 [10.1080/14786419.2017.1354191].

Synthesis of potential HIV integrase inhibitors inspired by natural polyphenol structures

Macchi B.;Frezza C.;
2018-01-01

Abstract

Drawing inspiration from the structural features of some natural polyphenols, the synthesis of two different model compounds as potential inhibitors of HIV integrase (IN) has been described. The former was characterised by a diketo acid (DKA) bioisostere, such as a β-hydroxycarbonyl moiety, between two fragments containing aromatic groups, while in the latter an epoxide linked two polyoxygenated aromatic residues. The moieties present in the structures are thought to function by chelating divalent metal ions on the enzyme catalytic site. Overall, 10 compounds were prepared and some of that submitted to molecular modelling studies (to investigate their interactions with the active site of IN), to metal titration studies (to detect their chelating capability) and to biological assays.
2018
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore CHIM/06 - CHIMICA ORGANICA
Settore CHIM/08 - CHIMICA FARMACEUTICA
English
DKA inhibitors; HIV integrase; Inhibitors; polyphenols; Catalytic Domain; Chelating Agents; HIV Integrase; HIV Integrase Inhibitors; Humans; Metals; Polyphenols; Structure-Activity Relationship; Models, Molecular
Righi, G., Pelagalli, R., Isoni, V., Tirotta, I., Marini, M., Palagri, M., et al. (2018). Synthesis of potential HIV integrase inhibitors inspired by natural polyphenol structures. NATURAL PRODUCT RESEARCH, 32(16), 1893-1901 [10.1080/14786419.2017.1354191].
Righi, G; Pelagalli, R; Isoni, V; Tirotta, I; Marini, M; Palagri, M; Dallocchio, R; Dessi, A; Macchi, B; Frezza, C; Forte, G; Dalla Cort, A; Portalone, G; Bovicelli, P
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
Righi Synthesis of potential HIV integrase inhibitors inspired by natural polyphenol structuresJNatProducts.pdf

solo utenti autorizzati

Descrizione: articolo principale
Licenza: Copyright dell'editore
Dimensione 1.51 MB
Formato Adobe PDF
1.51 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/2108/208959
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 4
social impact