[New nucleoside conjugates with phospholipids: synthesis of anti-HIV activity of rac-1-hexadecyl-2-acyl-sn-glycero-3-phosphonucleosides].

S I Malekin, Iu L Krugliak, N Iu Khromova, M Iu Aksenova, V P Sokolov, A V Kisin, T I Novozhilova, S G Popova, V K Kurochkin, G G Miller, L N Pokidysheva

Index: Bioorg. Khim. 23(8) , 648-54, (1997)

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Abstract

New nucleoside-phospholipid conjugates were synthesized based on 1,2-disubstituted glycerides and nucleosides. These contain rac-1-hexadecyl-2-palmitoyl(or 2-methylcarbamoyl)-sn-glycero-3-phosphate as the phospholipid component and 2',3'-didehydro-3'-deoxythymidine, 1-(Z-5-hydroxypentene-2-yl)thymine, or 2',3'-isopropylideneuridine as a nucleoside component. The conjugates were synthesized by three different ways: from rac-1-hexadecyl-2-acyl-sn-glycero-3-phospodichlorides, -3-phosphatidic acids, or -3-H-phosphonates. When subjected to mild alkaline hydrolysis, conjugates containing a 2-palmitoyl group formed conjugates with the lysophospholipid component that had not yet been described. All the conjugates obtained were amorphous compounds stable at room temperature. Their hemolytic and anti-HIV activities were determined. Some conjugates were found to completely inhibit in vitro HIV-1 reproduction in lower doses than the corresponding nucleosides.