SYNTHESIS, CHARACTERIZATION, AND BIOLOGICAL-ACTIVITY OF A NEW POTENT CLASS OF ANTI-HIV AGENTS, THE PEROXONIOBIUM-SUBSTITUTED HETEROPOLYTUNGSTATES

The mono- and trisubstituted peroxyniobium polyxyniobium polyoxotungst ates of formulas [(CH3)3NH]7[Si(NbO2)3W9O37], Cs7[Si(NbO2)3W9O37], alp ha-K5[Si(NbO2)W11O39] and alpha-[(CH3)3NH]5[Si(NbO2)W11O39], have been prepared, purified, and characterized spectroscopically by Si-29 NMR, W-183 NMR, and IR. The presence of peroxo groups was verified by the yellow color of the product and quantified by iodometric titration. Th e potency of both the complexes and the precursor complexes was evalua ted in human peripheral blood mononuclear cells (PBMC) acutely infecte d with human immunodeficiency virus type 1 (HIV-1). Hexaniobate (K7H[N b6O19]) was the least effective with a median effective concentration (EC50) Of >100 muM, while CS7[Si(NbO2)3W9O37] was one of the most effe ctive compounds with an EC50 of 1.0 muM. None of the compounds were to xic to uninfected PBMC with the exception of alpha-K8[SiW11O39], which had a median inhibitory concentration (IC50) of 79 muM. The potency a nd selectivity of the complexes against HIV-1 reverse transcriptase wa s also evaluated and shown to be quite high (IC50 Values from 0.03 to 0.06 muM). The trimethylammonium salts of the complexes were tested fo r their ability to inhibit the interaction between gp120 and CD4 using a cell-free system. The complex [(CH3)3NH]7[Si(NbO2)3W9O37] inhibited this interaction by 70% at 25 muM.