title: Prenyloxyphenylpropanoids as novel lead compounds for the selective inhibition of geranylgeranyl transferase I.
abstract: 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.
authors.affiliation: Dipartimento di Scienze del Farmaco, Via dei Vestini 31, 66013 Chieti Scalo (CH), Italy. fepifano@unich.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Epifano
authors.forename: Massimo
authors.initials: M
authors.lastname: Curini
authors.forename: Salvatore
authors.initials: S
authors.lastname: Genovese
authors.forename: Michelle
authors.initials: M
authors.lastname: Blaskovich
authors.forename: Andrew
authors.initials: A
authors.lastname: Hamilton
authors.forename: Said M
authors.initials: SM
authors.lastname: Sebti
mesh_terms: 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
chemical_list: 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