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Synthesis of a fluorescent analogue of methotrexate lipophilic prodrug

Abstract

A fluorescent analogue of the lipophilic prodrug of antitumor agent methotrexate has been synthesized. The conjugate consists of a residue of rac-1-[13-(Me4-BODIPY-8)tridecanoyl]-2-oleoylglycerol connected to methotrexate by an ester bond via β-Ala-N-carbonylmethylene linker (Me4-BODIPY-8 stands for 4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene-8-yl). The probe is designed for incorporation in the membrane of the liposomal vehicle to study a mechanism of interaction with tumor cells and intracellular traffic.

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Abbreviations

MTX:

methotrexate

MTX-DG:

rac-1,2-dioleoylglyceride conjugate of MTX

DHFR:

dihydrofolate reductase

RFC:

reduced folate carrier

Me4-BODIPY-8, or BDP:

4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene-8-yl

Gro:

glycerol

Ole:

oleoyl (9Z-heptadecenyl-17-carbonyl)

TEA:

triethylamine

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Correspondence to E. L. Vodovozova.

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Original Russian Text © Yu.V. Vlasenko, A.S. Alekseeva, E.L. Vodovozova, 2014, published in Bioorganicheskaya Khimiya, 2014, Vol. 40, No. 1, pp. 125–128.

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Vlasenko, Y.V., Alekseeva, A.S. & Vodovozova, E.L. Synthesis of a fluorescent analogue of methotrexate lipophilic prodrug. Russ J Bioorg Chem 40, 114–117 (2014). https://doi.org/10.1134/S1068162014010129

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  • DOI: https://doi.org/10.1134/S1068162014010129

Keywords

  • methotrexate
  • lipophilic prodrugs
  • liposomes
  • BODIPY label