Synthesis, characterization, and anti-human immunodeficiency virus activity of water-soluble salts of polyoxotungstate anions with covalently attached organic groups.
The cesium and tetramethylammonium (TMA) salts of polyoxotungstate anions with covalently attached organosilyl groups of formula [(RSi)2O]SiW11O39(4-), where R = CH2CH2COCH3, (CH2)3CN, and CH==CH2 (1-R, cesium salt, unless otherwise noted) have been prepared, purified, and spectroscopically characterized. The water solubility (25 degrees C) of these 10 new compounds ranges from 0.14 mM to 2.16 mM. All appear to be stable in aqueous media over a period of several hours as assessed by 1H NMR. The activities (EC50) of the new compounds against human immunodeficiency virus in primary human lymphocytes range from 3.3 microM to 39.0 microM. Their toxicities (IC50) are all greater than 100 microM. The inhibition constants of the new compounds against purified virion-derived HIV-1 reverse transcriptase are in the 1-10 microM range.
Weeks
M S
MS
Department of Chemistry, Emory University, Atlanta, Georgia 30322.
Hill
C L
CL
Schinazi
R F
RF
D000838:Anions; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D002478:Cells, Cultured; D004355:Drug Stability; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011108:Polymers / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D018894:Reverse Transcriptase Inhibitors; D012995:Solubility; D014414:Tungsten / Q000494:pharmacology / Q000633:toxicity; D014867:Water
D000838:Anions; D000998:Antiviral Agents; D011108:Polymers; D018894:Reverse Transcriptase Inhibitors; D014867:Water; D014414:Tungsten