Synthesis and virucidal activity of a water-soluble, configurationally stable, derivatized C60 fullerene.
The bis(monosuccinimide) derivative of p,p'-bis(2-aminoethyl)diphenyl-C60 (compound 1), prepared by the fulleroid route, is active against human immunodeficiency virus type 1 (HIV-1) and HIV-2 (50% effective concentration [EC50] averaging approximately 6 microM) in acutely or chronically infected human lymphocytes and is active in vitro against 3'-azido-3'-deoxythymidine-resistant HIV-1 (EC50, approximately 3 microM). The virucidal properties of compound 1 were confirmed by virus inactivation assays. Compound 1 was noncytotoxic up to 100 microM in peripheral blood mononuclear cells and H9, Vero, and CEM cells. In cell-free assays, whereas the fullerene showed comparable activity against HIV-1 reverse transcriptase and DNA polymerase alpha (50% inhibitory concentration of approximately 5 microM), it demonstrated selective activity against HIV-1 protease.
Schinazi
R F
RF
Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322.
Sijbesma
R
R
Srdanov
G
G
Hill
C L
CL
Wudl
F
F
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002244:Carbon / Q000737:chemistry* / Q000494:pharmacology*; D002478:Cells, Cultured; D004355:Drug Stability; D037741:Fullerenes; D015497:HIV-1; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D037741:Fullerenes; D002244:Carbon; C069837:fullerene C60