Synthesis and antiproliferative activity of N-acylaspartic acid dimethyl esters.
Farnesyl residues are found as a lipophilic modification of a number of important proteins. In addition, synthetic farnesyl derivatives display a range of biological effects. We have prepared a series of N-acylaspartates as structural analogs of farnesylpyrophosphate in which the farnesyl residue has been replaced by a number of different aliphatic and aromatic carboxylic acids and the aspartate is used as a pyrophosphate surrogate. The corresponding dimethyl esters of these aspartates were assayed against different tumor cell lines. Several N-acylaspartic acid dimethyl esters carrying an aromatic acyl residue displayed a selective antiproliferative effect against THP-1 cells with GI50 values ranging from 7.6 to 1.3 microM.
Schlitzer
M
M
Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Germany. schlitze@mailer.uni-marburg.de
Sattler
I
I
Dahse
H M
HM
D000215:Acylation; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004952:Esters; D051231:Farnesyltranstransferase; D006131:Growth Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D011106:Polyisoprenyl Phosphates / Q000737:chemistry / Q000494:pharmacology; D017368:Protein Prenylation; D011499:Protein Processing, Post-Translational; D012717:Sesquiterpenes; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D004952:Esters; D006131:Growth Inhibitors; D009363:Neoplasm Proteins; D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; D001224:Aspartic Acid; C004808:farnesyl pyrophosphate; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase