[New nucleoside conjugates with phospholipids: synthesis of anti-HIV activity of rac-1-hexadecyl-2-acyl-sn-glycero-3-phosphonucleosides].
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.
Malekin
S I
SI
Krugliak
Iu L
IuL
Khromova
N Iu
NIu
Aksenova
M Iu
MIu
Sokolov
V P
VP
Kisin
A V
AV
Novozhilova
T I
TI
Popova
S G
SG
Kurochkin
V K
VK
Miller
G G
GG
Pokidysheva
L N
LN
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D006868:Hydrolysis; D007124:Immunoenzyme Techniques; D009705:Nucleosides / Q000737:chemistry* / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry*; D018119:Stavudine / Q000737:chemistry; D013941:Thymine / Q000031:analogs & derivatives / Q000737:chemistry; D014529:Uridine / Q000031:analogs & derivatives / Q000737:chemistry; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D009705:Nucleosides; D010743:Phospholipids; C074310:2',3'-O-isopropylidene uridine; D018119:Stavudine; D013941:Thymine; D014529:Uridine
Novye kon"iugaty nukleozidov i anti-VICH-aktivnost' rac-1-geksadetsil-2-atsil-sn-glitsero-3-fosfonuckleozidov.