Synthesis and Activity of New Epipolythiopiperazine-2,5-dione Compounds. I.

Abstract

The new lipophilic epipolythiopiperazine-2,5-diones 1,4-dibutylepidithiopiperazine-2,5-dione. 1,4-dibenzylepidithiopiperazine-2,5-dione, 1-benzyl-4-methylepidithiopiperazine-2,5-dione and 3,3′-dithiobis(1,4-dimethylpiperazine-2,5-dione) were synthesized. Unlike the parent compound, the fungal toxin and immunomodulating agent gliotoxin, these compounds did not affect macrophage adherence and cell proliferation in vitro. Like the reduced form of gliotoxin and other simple analogues, these new compounds induce oxidative damage to naked DNA. We conclude that an increase in lipophilicity plays no part in the biological activity of these compounds and in fact abrogates almost all activity. We also synthesized an intermolecular disulfide analogue which also lacked activity.