TY - JOUR
T1 - Phenol-derived CVFM analog inhibitors of Ras farnesyltransferase possessing cellular in vitro activity
AU - Caliendo, Giuseppe
AU - Fiorino, Ferdinando
AU - Grieco, Paolo
AU - Perissutti, Elisa
AU - Ramunno, Anna
AU - Santagada, Vincenzo
AU - Albrizio, Stefania
AU - Califano, Daniela
AU - Giuliano, Ada
AU - Santelli, Giovanni
PY - 1998
Y1 - 1998
N2 - A study was performed on structure-activity relationships of a series of phenol-derived, CVFM analogs, inhibitors of Ras Farnesyltransferase (FTase). The effect of various substituents on the phenol ring was examined, while the VFM moiety of the potent inhibitor CVFM was kept constant. The FTase inhibitory activity, reported as IC50 in table I, was influenced by both the chemical properties and the relative position of the substituents on the phenolic ring. The most active compounds in this series contained a chloro or bromine substituent on the phenolic ring. Subsequently we have tested the effects of these FTase inhibitors on the anchorage-dependent growth of two rat epithelial cell lines, FRTL-5 and the same line v-Ha-ras transformed. While most of the compounds were inactive, two showed a growth inhibitory effect: compound 4 was active against normal as well against transformed cells while derivative 13 was active only against transformed cells.
AB - A study was performed on structure-activity relationships of a series of phenol-derived, CVFM analogs, inhibitors of Ras Farnesyltransferase (FTase). The effect of various substituents on the phenol ring was examined, while the VFM moiety of the potent inhibitor CVFM was kept constant. The FTase inhibitory activity, reported as IC50 in table I, was influenced by both the chemical properties and the relative position of the substituents on the phenolic ring. The most active compounds in this series contained a chloro or bromine substituent on the phenolic ring. Subsequently we have tested the effects of these FTase inhibitors on the anchorage-dependent growth of two rat epithelial cell lines, FRTL-5 and the same line v-Ha-ras transformed. While most of the compounds were inactive, two showed a growth inhibitory effect: compound 4 was active against normal as well against transformed cells while derivative 13 was active only against transformed cells.
KW - Cellular in vitro activity
KW - Phenol derivative
KW - Ras Farnesyltransferase inhibitor
UR - http://www.scopus.com/inward/record.url?scp=0032440933&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032440933&partnerID=8YFLogxK
U2 - 10.1016/S0223-5234(98)80031-7
DO - 10.1016/S0223-5234(98)80031-7
M3 - Article
AN - SCOPUS:0032440933
VL - 33
SP - 725
EP - 732
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
IS - 9
ER -