Linked Life Data

11356105

Source:http://linkedlifedata.com/resource/pubmed/id/11356105

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2001-5-17
pubmed:abstractText
The 1-O-hexadecyl-2-O-methyl-sn-glyceryl phosphodiester AZT 4 and hexadecyl-phosphodiester AZT 5 derivatives were synthesized and found to be active against HIV-1, HIV-2, and tumor cell proliferation. Compared to AZT, compound 4 possessed ca. 10-fold lower anti-HIV activity and ca. 10-fold higher anti-tumor cell activity. Compound 5 was 10-fold less potent than compound 4 in both biological tests. In an attempt to correlate biological activity of compounds 4 and 5 with structure, their conformational and thermal effects on membrane bilayers were compared using a combination of NMR spectroscopy, computational analysis, and Differential Scanning Calorimetry. The obtained results showed that compound 4 adopts a compact conformation in which the alkyl chain, the 2-methoxyglyceryl functionality, and the methyl group of thymine are in spatial proximity, while analogue 5 possesses a less compact conformation of the nucleoside base and the alkyl chain. The presence of the 2-methoxyglyceryl group in compound 4 may augment its potency by inducing a turn of the alkyl chain stabilized by hydrophobic interactions. The DSC scans show that conjugate 4 affects less effectively the thermotropic properties of model membrane bilayers than compound 5. This may be attributed to the fact that compound 4 is incorporated in a compact conformation and does not perturb significantly the trans:gauche isomerization of the membrane phospholipids. In contrast, conjugate 5 may enter with a less compact conformation and perturb more the membrane bilayers.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1702-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11356105-Animals, pubmed-meshheading:11356105-Anti-HIV Agents, pubmed-meshheading:11356105-Antineoplastic Agents, pubmed-meshheading:11356105-Calorimetry, Differential Scanning, pubmed-meshheading:11356105-Cells, Cultured, pubmed-meshheading:11356105-Dideoxynucleotides, pubmed-meshheading:11356105-Drug Screening Assays, Antitumor, pubmed-meshheading:11356105-Glycerol, pubmed-meshheading:11356105-HIV-1, pubmed-meshheading:11356105-HIV-2, pubmed-meshheading:11356105-Humans, pubmed-meshheading:11356105-Lipid Bilayers, pubmed-meshheading:11356105-Magnetic Resonance Spectroscopy, pubmed-meshheading:11356105-Mice, pubmed-meshheading:11356105-Models, Molecular, pubmed-meshheading:11356105-Molecular Conformation, pubmed-meshheading:11356105-Nucleosides, pubmed-meshheading:11356105-Solutions, pubmed-meshheading:11356105-T-Lymphocytes, pubmed-meshheading:11356105-Thymidine Kinase, pubmed-meshheading:11356105-Zidovudine
pubmed:year
2001
pubmed:articleTitle
Ether phospholipid-AZT conjugates possessing anti-HIV and antitumor cell activity. Synthesis, conformational analysis, and study of their thermal effects on membrane bilayers.
pubmed:affiliation
National Hellenic Research Foundation, Institute of Organic and Pharmaceutical Chemistry, Vas. Constantinou 48, 116 35, Athens, Greece.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't