Isochromophilones I and II, Novel Inhibitors against gp120-CD4 Binding Produced by Penidllium multicolor FO-2338

I. Screening, Taxonomy, Fermentation, Isolation and Biological Activity

Abstract

Isochromophilones I and II, the first novel gp120-CD4 binding inhibitors of microbial origin, were isolated from a cultured broth of a soil fungus designated as Penidllium multicolor FO-2338. These compounds were obtained as yellow powders from the cultured broth together with the known related compounds sclerotiorin, ochrephilone and rubrorotiorin. Isochromophilones I and II (C₂₃H₂₅O₂₅Cl and C₂₂H₂₇O₄Cl, respectively) have an azaphilone skeleton and a chlorine atom. Isochromophilones strongly inhibited gp120-CD4 binding (IC₅₀: 6.6 and 3.9μM, respectively), but the other related compounds did not. Isochromophilone II inhibited significantly HIV replication in peripheral human lymphocytes at 25 μM.