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.