Uptake and fate of water-soluble, nondegradable polymers with antiviral activity in cells and animals

Abstract

Poly(9-vinyladenine) and poly(1-vinyluracil) which are nondegradable, soluble polymers are taken up partially by mammalian cells grown in culture. The polymers remain associated with cells for several generations. In mice, after ip application, polymers slowly accumulate in liver, spleen, and thymus and remain there for as long as a month. Thus, these polymers which suppress the replication of murine leukemia viruses also accumulate in organs where the virus replicates. However, their antiviral activity does not reflect the amount of polymer found in these animal tissues. We propose that the polymers are gradually segregated into a group of cells or into subcellular organelles away from primary sites of virus replication. The results suggest that for a directly acting polymeric drug, a half-life over 24 h is without advantage.

Mimicry of Biological Macromolecules by Polyaromatic Anionic Compounds

“…The synthesis of polymer 5 (Scheme 1) began with the treatment of 6,7-dimethoxy-3-isochromanone (13) with methanolic HBr Scheme 1. Reagents: (a) MeOH/HBr, (b) SnHŒu}/AIBN/toluene/reflux, (c) BBrJCH1Cl1.…”

“…Several classes of polymers have been prepared to provide macromolecules with biological activity [8]. These include aurintricarboxylic acid (ATA), 3 ( Figure 1) [9][10][11][12], poly(9-vinyladenine) [13], poly(l-vinyluracil) [13], pyran copolymer [14], chloramphenicol ester of maleic acid and 10-undecendyl copolymer [15], poly-N-oxides [16], copolymer with formaldehyde and sulfapyridine [17], copolymer with urea and formaldehyde [18] and polyacrylamide sialic acid copolymer [19]. ATA has been extensively studied and exhibits a variety of biological activities including the inhibition of enzynies binding to nucleic acids (DNA polymerase [20][21][22], RNA polymerase [23][24][25], ribonucleases [26][27][28]), the inhibition of ristocetin or shear stress induced vWF mediated platelet aggregation [29,30], inhibition of cytopathic effects of HIV 1 [31], prevention of binding of interferon to its receptor [32] and binding to polynucleotide domains of glucocorticoid receptors [33] and dihydroxyvitamin D3 receptors [34].…”

Polymers in the Medical Antiviral Front-Line

“…Pitha et al researched the antiviral effect of amine-containing polymers. They showed that both poly(9-vinyladenine) and poly(l-vinyluracil) exhibited better antiviral properties, compared to commercial antiviral drugs [106].…”