Non-thiol farnesyltransferase inhibitors: N-(4-aminoacylamino-3-benzoylphenyl)-3-[5-(4-nitrophenyl)-2 furyl]acrylic acid amides and their antimalarial activity.
Water solubility was previously found to be essential for in vivo-antimalarial activity of a novel type of benzophenone-based farnesyltransferase inhibitors. Introduction of a alpha-amino group into the phenylacetic acid substructure provided more soluble compounds with high farnesyltransferase inhibitory activity. The in vitro-antimalarial activity was detrimentally influenced by this structural modification.
Kettler
Katja
K
Department für Pharmazie, Zentrum für Pharmaforschung, Ludwig-Maximilians Universität München, Butenandtstrasse 5-13, 81377 München, Germany.
Wiesner
Jochen
J
Silber
Katrin
K
Haebel
Peter
P
Ortmann
Regina
R
Sattler
Isabel
I
Dahse
Hans-Martin
HM
Jomaa
Hassan
H
Klebe
Gerhard
G
Schlitzer
Martin
M
D000178:Acrylamides / Q000138:chemical synthesis* / Q000494:pharmacology; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051231:Farnesyltranstransferase; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development; D012995:Solubility; D013329:Structure-Activity Relationship
D000178:Acrylamides; D000962:Antimalarials; D004791:Enzyme Inhibitors; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase