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Synthesis of a Lipid Derivative of the Antitumor Agent Methotrexate


A lipophilic methotrexate prodrug capable of incorporation into membranes of carrier liposomes was synthesized. The conjugate consists of a lipophilic rac-1,2-dioleoylglycerol anchor connected to methotrexate through a βAla–N-carbonylmethylene linker, which should be located in the polar region of the lipid bilayer. The ester bond between the hydrophilic linker and the antitumor agent can be hydrolyzed by intracellular esterases. The liposomal formulation of the prodrug exhibited a cytotoxic activity in vitro.

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Vodovozova, E.L., Evdokimov, D.V. & Molotkovsky, J.G. Synthesis of a Lipid Derivative of the Antitumor Agent Methotrexate. Russian Journal of Bioorganic Chemistry 30, 599–601 (2004).

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  • methotrexate
  • lipophilic prodrugs
  • liposomes