Stable propylphosphonic acid analogues of geranylgeranyl diphosphate possessing inhibitory activity on geranylgeranyl protein transferase

Filippo Minutolo; Valentina Asso; Simone Bertini; Laura Betti; Gianbattista Gervasi; Elisa Ghilardi; Gino Giannaccini; Giorgio Placanica; Giovanni Prota; Simona Rapposelli; Marco Macchia

doi:10.1016/j.farmac.2004.06.003

Stable propylphosphonic acid analogues of geranylgeranyl diphosphate possessing inhibitory activity on geranylgeranyl protein transferase

Farmaco. 2004 Nov;59(11):857-61. doi: 10.1016/j.farmac.2004.06.003.

Authors

Filippo Minutolo¹, Valentina Asso, Simone Bertini, Laura Betti, Gianbattista Gervasi, Elisa Ghilardi, Gino Giannaccini, Giorgio Placanica, Giovanni Prota, Simona Rapposelli, Marco Macchia

Affiliation

¹ Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.

PMID: 15544789
DOI: 10.1016/j.farmac.2004.06.003

Abstract

Stable analogues of geranylgeranyl diphosphate, possessing 3-(phosphono)propionamido moieties in the place of the metabolically unstable diphosphate portion, were prepared and submitted to prenyltransferase (GGTase and FTase) inhibition assays. In one case, an excellent GGTase inhibitory activity was obtained (IC(50) = 39 nM), accompanied by a certain degree of GGTase vs. FTase selectivity.

MeSH terms

Alkyl and Aryl Transferases / antagonists & inhibitors*
Diterpenes / chemical synthesis*
Enzyme Inhibitors / pharmacology
Inhibitory Concentration 50
Organophosphonates / chemical synthesis*
Organophosphonates / pharmacology
Polyisoprenyl Phosphates / chemical synthesis*

Substances

Diterpenes
Enzyme Inhibitors
Organophosphonates
Polyisoprenyl Phosphates
Alkyl and Aryl Transferases
geranylgeranyltransferase type-I
p21(ras) farnesyl-protein transferase
geranylgeranyl pyrophosphate