Prenyloxyphenylpropanoids as novel lead compounds for the selective inhibition of geranylgeranyl transferase I.
In this study, we synthesized some natural and semisynthetic prenyloxyphenylpropanoids (e.g., coumarins and cinnamic acid derivatives) and we assessed their in vitro inhibitory activity against farnesyl transferase (FTase) and geranylgeranyl transferase I (GGTase I). No compound was an effective inhibitor of FTase, while farnesyloxycinnamic acids were shown to selectively inhibit GGTase I with IC(50) values ranging from 28 to 39 microM.
Epifano
Francesco
F
Dipartimento di Scienze del Farmaco, Via dei Vestini 31, 66013 Chieti Scalo (CH), Italy. fepifano@unich.it
Curini
Massimo
M
Genovese
Salvatore
S
Blaskovich
Michelle
M
Hamilton
Andrew
A
Sebti
Said M
SM
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry*; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008968:Molecular Conformation; D010936:Plant Extracts / Q000378:metabolism
D000970:Antineoplastic Agents; D002934:Cinnamates; D003374:Coumarins; D004791:Enzyme Inhibitors; D010936:Plant Extracts; C029010:cinnamic acid; C030123:coumarin; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I