ISOCHROMOPHILONE-I AND ISOCHROMOPHILONE-II, NOVEL INHIBITORS AGAINST GP120-CD4 BINDING PRODUCED BY PENICILLIUM MULTICOLOR FO-2338 .1. SCREENING, TAXONOMY, FERMENTATION, ISOLATION AND BIOLOGICAL-ACTIVITY

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 Penicillium 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 (C23H25O5Cl and C22H27O4Cl, respectively) have an azaphilone skeleton and a chlorine atom. Isochromophilones strongly inhibited gp120-CD4 binding (IC50: 6.6 and 3.9 mu M, respectively), but the other related compounds did not. Isochromophilone II inhibited significantly HIV replication in peripheral human lymphocytes at 25 mu M.