Lipoamino acid conjugates of methotrexate with antitumor activity.
The synthesis, characterization, and in vitro antitumor activity against a wild and a transport-resistant CCRF-CEM cell line is described for a series of alpha,gamma-bisamide lipoamino acid and oligomer conjugates of methotrexate. The influence of the lipophilicity of the conjugates on the cytotoxicity and the dihydrofolate reductase inhibition was investigated. All compounds were more active than their fatty acid conjugate analogues. Compound le with a 12-carbon atom aliphatic side chain showed the highest in vitro activity.
Pignatello
R
R
The Department of Pharmaceutical and Biological Chemistry, The School of Pharmacy, University of London, UK.
Jansen
G
G
Kathmann
I
I
Puglisi
G
G
Toth
I
I
D000596:Amino Acids / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D005493:Folic Acid Antagonists / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008727:Methotrexate / Q000737:chemistry* / Q000494:pharmacology; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism
D000596:Amino Acids; D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate