Prenyloxyphenylpropanoids as novel lead compounds for the selective inhibition of geranylgeranyl transferase I

Francesco Epifano; Massimo Curini; Salvatore Genovese; Michelle Blaskovich; Andrew Hamilton; Said M Sebti

doi:10.1016/j.bmcl.2007.01.097

Prenyloxyphenylpropanoids as novel lead compounds for the selective inhibition of geranylgeranyl transferase I

Bioorg Med Chem Lett. 2007 May 1;17(9):2639-42. doi: 10.1016/j.bmcl.2007.01.097. Epub 2007 Feb 2.

Authors

Francesco Epifano¹, Massimo Curini, Salvatore Genovese, Michelle Blaskovich, Andrew Hamilton, Said M Sebti

Affiliation

¹ Dipartimento di Scienze del Farmaco, Via dei Vestini 31, 66013 Chieti Scalo (CH), Italy. fepifano@unich.it

PMID: 17314046
DOI: 10.1016/j.bmcl.2007.01.097

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.

MeSH terms

Alkyl and Aryl Transferases / antagonists & inhibitors*
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Chemistry, Pharmaceutical / methods*
Cinnamates / chemical synthesis
Cinnamates / chemistry*
Coumarins / chemical synthesis
Coumarins / chemistry*
Drug Design
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Inhibitory Concentration 50
Models, Chemical
Molecular Conformation
Plant Extracts / metabolism

Substances

Antineoplastic Agents
Cinnamates
Coumarins
Enzyme Inhibitors
Plant Extracts
cinnamic acid
coumarin
Alkyl and Aryl Transferases
geranylgeranyltransferase type-I