SULFONIC-ACID POLYMERS ARE POTENT INHIBITORS OF HIV-1 INDUCED CYTOPATHOGENICITY AND THE REVERSE TRANSCRIPTASES OF BOTH HIV-1 AND HIV-2

Four novel sulfonic acid polymers were evaluated for their in vitro HI V-1 and HIV-2 reverse transcriptase (RT) inhibitory activity and found to be equipotent against both RTs. The aromatic polymers demonstrated IC50 values that were approximately 10(3)-fold lower than those obser ved with the aliphatic polymers. Among the aromatic polymers, poly(4-s tyrenesulfonic acid) (PSS) (MW 8000; IC50 = 0.02 mug/ml) was 3-fold mo re potent than poly(anetholesulfonic acid) (PAS) of approximately the same molecular weight range. The activity of PSS polymers increased in proportion to the size of the polymers and, relative to suramin, acti vity could be enhanced over 200-fold. These polymers also inhibited th e cytopathic effect of HIV-1 at concentrations that were non-toxic to MT-4 cells. The potent RT inhibitory properties of these stable sulfon ic acid polymers suggest that structure-activity studies are warranted to yield agents capable of inhibiting multiple stages of the viral pr ocess.