In vitro Anti-HIV-1 Activity of sn-2-Substituted 1-O-Octadecyl-sn-Glycero-3-Phosphonoformate Analogues and Synergy with Zidovudine
| Autor: | Saskia E Hostetler, John W. Mellors, Douglas D. Richman, Karl Y. Hostetler, Hammond Jennifer, Ting-Chao Chou, James R. Beadle, Ganesh D. Kini, Kathy A. Aldern |
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| Rok vydání: | 2000 |
| Předmět: |
0301 basic medicine
Foscarnet Stereochemistry 030106 microbiology Ether Viral Plaque Assay Virus Replication Antiviral Agents 01 natural sciences 03 medical and health sciences chemistry.chemical_compound Zidovudine medicine Humans Alkyl chemistry.chemical_classification Drug Carriers Drug Synergism Biological activity General Medicine Prodrug 0104 chemical sciences Drug Combinations 010404 medicinal & biomolecular chemistry Ether lipid chemistry Foscarnet Sodium Liposomes HIV-1 HeLa Cells medicine.drug |
| Zdroj: | Antiviral Chemistry and Chemotherapy. 11:213-219 |
| ISSN: | 2040-2066 |
| Popis: | Monoalkyl ether lipid analogues of foscarnet (phosphonoformate, PFA) exhibit substantially greater in vitro antiviral activity than unmodified PFA against human immunodeficiency virus type 1 (HIV-1). Our previous studies indicate that the length of the alkyl chain must be 14–22 carbons for optimal antiviral activity. To further evaluate the structure-activity relationship, we prepared 1-O-octadecyl- sn-glycerol analogues of PFA with various substitutions at the sn-2 position of glycerol and determined the effect of structure on in vitro antiviral activity and selectivity against HIV-1 in MT-2 and CD4-expressing HeLa cells (HT4–6C). We also studied combinations of zidovudine with PFA, 1-O-octadecyl-2-O-methyl- sn-glycero-3-PFA, or 1-O-octadecyl- sn-glycero-3-PFA and calculated their combination index values against HIV-1 in HT4–6C cells. Alkyl substitutions of one to four carbons at the sn-2 position of glycerol showed optimal antiviral activity. Both alkyl ether lipid analogues were strongly synergistic with zidovudine over a wide range of drug ratios and concentrations. 1-O-octadecyl- sn-glycerol analogues of PFA have selective antiviral properties and warrant further evaluation as potential antiretroviral drugs. |
| Databáze: | OpenAIRE |
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