SUPPRESSION OF HIV INFECTION BY SUBSTITUTED MONOSACCHARIDES

CERTAIN SULFATED POLYSACCHARIDES AND DISACCHARIDES HAVE PROVED TO BE SELECTIVE INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS (HIV) TYPE 1. AMINOSUGAR DERIVATIVES HAVE ALSO EXHIBITED POTENTIAL ANTI-HIV ACTIVITY. THE PURPOSE OF THIS PROGRAM WILL BE TO DETERMINE WHETHER THE SULFATED AND ALKAMINO-SUBSTITUTED AND OTHERWISE SUBSTITUTED MONOSACCHARIDE DERIVATIVES CURRENTLY BEING DEVELOPED BY KENWOOD LABORATORIES, INC., EXHIBIT AN ANTI-HIV ACTION ANALOGOUS TO THAT OF DEXTRAN SULFATE, ONE OFTHE MOST POTENT OF THE ABOVE, WITHOUT EXHIBITING EMERGENT DEXTRAN SULFATE TOXICITY AND WITH IMPROVED BIOAVAILABILITY. TOWARD THIS END, RESEARCH EFFORTS WILL DETERMINE WHETHER IN A NOVEL FAMILY OF SUBSTITUTED SUGARS THERE EMERGE COMPOUNDS, FOLLOWING SULFATION, THAT WARRANT LABORATORY AND CLINICAL EVALUATION AS ANTI-HIV DRUGS. RELEVANT POLYSULFATED COMPOUNDS WILL BE SYNTHESIZED AND THEIR CYTOTOXICITY AND ANTI-HIV POTENTIAL WILL BE EVALUATED IN A MT-4 CELL SYSTEM IN WHICH VIRUS-PRODUCED CYTOPATHOLOGY AND VIRAL TITER ARE EVALUATED. ANTI-HIV EFFECTS OBTAINED WILL BE COMPARED WITH THOSE OF AZIDOTHYMIDINE (AZT) AND DEXTRAN SULFATE.