Anti-HIV-1 activity, toxicity, and stability studies of representative structural families of polyoxometalates

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Abstract
The anti-HIV-1 activity and toxicity of representative structural families of polyoxotungstates in human lymphocytes was determined. The 21 compounds examined include those derived from the following structural families: [NaSb9W21O86]18- (HPA-23), Xn+W12O40(8-n)- (Keggin), P2W18O626- (Wells-Dawson), W6O192- (Lindqvist), [NaP5W30O110]14- (Preyssler), and W10O324- (decatungstate). The molecular architecture of each of these structural families is constituted principally by a network of bonds between d0 WVI and oxide ions. Of these, 10 show median effective concentration (EC50) values of approximately 1 .mu.M and six have marked toxicity with a median inhibitory concentration (IC50) of less than 50 .mu.M. Only compounds containing more than six metal atoms showed appreciable antiviral activity. Beyond this, however, no marked correlation existed between the molecular size, charge, or charge density of the polyoxometalates and their anti-HIV-1 activity. Examination of an exemplary class of polyoxotungstates, the phosphotungstates of formula A- and B-PW9O349- under physiological conditions (buffered neutral aqueous media), illustrates that both isomers equilibrate rapidly to generate the same distribution of products and that this distribution depends principally on the buffer. These heretofore unappreciated complexities in the chemistry of these compounds under neutral aqueous conditions indicates interpretation or evaluation of these compounds in cell culture and other biological screens must be done with care.