Novel lead structures for antimalarial farnesyltransferase inhibitors.
Through the combination of nitrophenylfurylacryloyl moiety which has been designed to occupy an aryl binding site of farnesyltransferase with several AA(X)-peptidomimetic substructures some novel farnesyltransferase inhibitors were obtained. Evaluation of their antimalarial activity and some initial modifications yielded a 4-benzophenone- and a sulfonamid-based novel lead for antimalarial farnesyltransferase inhibitors.
Kettler
K
K
Department für Pharmazie, Zentrum für Pharmaforschung, Ludwig-Maximilians-Universität München, Germany.
Sakowski
J
J
Wiesner
J
J
Ortmann
R
R
Jomaa
H
H
Schlitzer
M
M
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000588:Amines / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051231:Farnesyltranstransferase; D009682:Magnetic Resonance Spectroscopy; D009574:Nitro Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D012441:Saccharomyces cerevisiae / Q000201:enzymology
D000588:Amines; D000962:Antimalarials; D004791:Enzyme Inhibitors; D009574:Nitro Compounds; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase