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 muM) in acutely or chronically infected human lymphocytes and is active in vitro against 3'-azido-3'-deoxythymidine-resistant HIV-1 (EC50, approximately 3 muM). The virucidal properties of compound 1 were confirmed by virus inactivation assays. Compound 1 was noncytotoxic up to 100 muM 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 muM), it demonstrated selective activity against HIV-1 protease.