Phosphonomethylphosphorylmethyl(oxy)-analogues of geranylgeranyl diphosphate as stable and selective geranylgeranyl protein transferase inhibitors.
The diphosphate moiety of geranylgeranyldiphosphate (GGdP) was replaced with metabolically and hydrolytically stable analogous polar portions, in an attempt to obtain new geranylgeranyltransferase (GGTase) inhibitors, which could also be selective over congener enzyme farnesyltransferase (FTase). In particular, the phosphonomethylphosphorylmethoxy derivative showed the highest inhibition potency, accompanied by a satisfactory GGTase/FTase selectivity.
Minutolo
Filippo
F
Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
Antonello
Michela
M
Barontini
Silvia
S
Bertini
Simone
S
Betti
Laura
L
Danesi
Romano
R
Gervasi
Gianbattista
G
Giannaccini
Gino
G
Papi
Chiara
C
Placanica
Giorgio
G
Rapposelli
Simona
S
Macchia
Marco
M
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D004224:Diterpenes / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D011106:Polyisoprenyl Phosphates / Q000138:chemical synthesis* / Q000494:pharmacology
D004224:Diterpenes; D004791:Enzyme Inhibitors; D009943:Organophosphorus Compounds; D011106:Polyisoprenyl Phosphates; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; C002963:geranylgeranyl pyrophosphate