Synthesis of a Lipid Derivative of the Antitumor Agent Methotrexate

Authors: E. L. Vodovozova¹; D. V. Evdokimov²; Jul. G. Molotkovsky²

Source: Russian Journal of Bioorganic Chemistry, Volume 30, Number 6, November 2004 , pp. 599-601(3)

Publisher: MAIK Nauka/Interperiodica

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Abstract:

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 beta

Ala–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.

Keywords: methotrexate; lipophilic prodrugs; liposomes

Document Type: Research article

DOI: http://dx.doi.org/10.1023/B:RUBI.0000049779.60159.c5

Affiliations: 1: Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997 Russia elvod@ibch.ru, Email: elvod@ibch.ru 2: Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997 Russia

Publication date: 2004-11-01