A promising approach to enhancing the bioavailability of hydrophilic therapeutic agents including anti-HIV nucleosides is designing their pseudotriglyceride derivatives that may mimic natural lipids and take advantage of their metabolic pathways resulting in improved delivery to target cells. The synthesis of a series of new 1,3-diglycerides and AZT conjugates employing various linkage types between the pharmacophore residue and the spacer part of the hydrophobic moiety (ester or phosphodiester) is described. The hydrolytic properties of the synthesized liponucleosides (in buffer solutions and under the action of pancreatic lipase) have been studied. Liposomes based on these AZT-containing prodrugs have been obtained.
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The work was supported financially by the Analytical Ministerial Targeted Program “Development of the Scientific Potential of Graduate Schools, 2009 – 2011,” RF Federal Agency for Education (Project No. 2.1.1/2715).
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Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 44, No. 10, pp. 27 – 34, October, 2010.
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Lonshakov, D.V., Baranova, E.O., Lyutik, A.I. et al. Synthesis and properties of 3′-azido-3′-deoxythymidine derivatives of glycerolipids. Pharm Chem J 44, 557–563 (2011). https://doi.org/10.1007/s11094-011-0517-y
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DOI: https://doi.org/10.1007/s11094-011-0517-y