Inhibition of tat-mediated HIV-1-LTR transactivation and virus replicationby sulfhydryl compounds with chelating properties

D-Penicillamine, a structural analog of cysteine, has the ability to chelat e metal ions and reacts with cysteine. We have shown earlier that D-Penicil lamin is a potential inhibitor of tat-mediated transactivation of HIV-1-LTR (14) and posesses anti-HIV-1 activity (23). Following this approach, we ev aluated the anti-tat and anti-HIV-1 activity of several sulfhydryl compound s with chelating properties. The tested compounds: N-(2-Mercapto-propionyl) -glycin (MPG), 2,3-Dimercapto-propanol (DMP) and 2,3-Dimercapto-propane-sul fonic acid (DMPS) exhibited an inhibitory effect on the tat-mediated transa ctivation in Jurkat cells, as well as in U937 cells. The highest inhibitory response was shown by DMP leading to about 50% inhibition of transactivati on in Jurkat cels and art 80% inhibition in U937 cells. On the contrary, DM PS (30 mu g/ml) had no inhibitory effect in U937 cells, but did exhibit a 5 0% inhibition of transactivation in Jurkat cells at 30 mu g/ml. The antivir al activity of DMP and DMPS was evaluated in H9 cells. In the concentration range which is effective for antiviral effect, both the compounds were hig hly cytotoxic. Mercapto-propionyl-glycin, although a weak inhibitor of tran sactivation, was able to inhibit synctia formation to more than 90% and inh ibit the viral antigene expression to about 70%. The concentration of MPG n eeded to achieve this antiviral effect was very high, but it had no cytotox icity at this concentration. We suggest that a search for compounds using t his approach may be useful in developing potential inhibitors of tat-mediat ed transactivation.