Malekin S I, Krugliak Iu L, Khromova N Iu, Aksenova M Iu, Sokolov V P, Kisin A V, Novozhilova T I, Popova S G, Kurochkin V K, Miller G G, Pokidysheva L N
Bioorg Khim. 1997 Aug;23(8):648-54.
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.
基于1,2 - 二取代甘油酯和核苷合成了新的核苷 - 磷脂缀合物。这些缀合物含有外消旋 - 1 - 十六烷基 - 2 - 棕榈酰基（或2 - 甲基氨基甲酰基） - sn - 甘油 - 3 - 磷酸作为磷脂成分，以及2',3' - 二脱氢 - 3' - 脱氧胸苷、1 - (Z - 5 - 羟基戊烯 - 2 - 基)胸腺嘧啶或2',3' - 异亚丙基尿苷作为核苷成分。缀合物通过三种不同方法合成：由外消旋 - 1 - 十六烷基 - 2 - 酰基 - sn - 甘油 - 3 - 磷酰二氯、 - 3 - 磷脂酸或 - 3 - H - 膦酸酯合成。当进行温和碱性水解时，含有2 - 棕榈酰基的缀合物形成了尚未有描述的与溶血磷脂成分的缀合物。所得到的所有缀合物均为在室温下稳定的无定形化合物。测定了它们的溶血和抗HIV活性。发现一些缀合物在比相应核苷更低的剂量下能完全抑制体外HIV - 1的复制。
