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• W2000766004 abstract "Lipophilic methotrexate (MTX)–lipoamino acid conjugates coupled with amide or ester linkages (1a–1r) were synthesised. The inhibitory activity of the conjugates was evaluated on bovine liver DHFR. The in vitro growth inhibitory effect against MTX-sensitive human lymphoblastoid CCRF-CEM cells and an MTX-resistant sub-line (CEM/MTX), which displays defective intracellular transport of MTX, was determined under short-term and continuous (120-h incubation) exposure conditions. The α, γ, or α,γ amide conjugates showed different activity in inhibiting the growth of parent cells. CEM/MTX cells were much less susceptible than CCRF-CEM cells to inhibition by α or α,γ-substituted lipoamino acid conjugates, whereas both cell lines were almost equally sensitive to the MTX-γ conjugates. Although less potent than MTX, they could partially circumvent the impaired transport system. These findings confirm that lipophilic MTX conjugates may be good lead compounds on the drug development for the treatment of some MTX-resistant tumors. Ester-type conjugates displayed an interesting activity against parent CCRF-CEM cells, although they were less potent against the transport-resistant sub-line. Stability studies on these molecules indicated that they are not degraded into MTX in the culture medium, thus suggesting that they are not able to over-cross cell resistance despite of their lipophilicity." @default.
• W2000766004 created "2016-06-24" @default.
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• W2000766004 date "2000-05-01" @default.
• W2000766004 modified "2023-10-05" @default.
• W2000766004 title "Lipophilic methotrexate conjugates with antitumor activity" @default.
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• W2000766004 doi "https://doi.org/10.1016/s0928-0987(00)00062-2" @default.
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