Delaminomycin B

In order to develop a new class of low molecular weight immunomodulators for the treatment of incurable diseases involving cancer, hematologic diseases and inflammation, we have sought cytokine inducers and inhibitors of cell adhesion to the extracellular matrix among the low molecular compounds produced by microorganisms. Cytogenin, cytoblastin (a monokine inducer), conagenin (a lymphokine inducer) and delaminomycins and IC-101 (inhibitors of cell adhesion to extracellular matrices) have been recently found in our institute. In this report, we describe the principles of screening and structures, and discuss their biological activities.

Delaminomycins A, B, C and their derivatives were prepared and investigated biological activities of them. Among these compounds, spiro compounds (A2, B2 and C2) showed stronger inhibitory activity than natural products (A1, B1 and C1) on B16 melanoma cells adhesion assay and Con A-induced proliferation of murine splenic lymphocytes assay. In MLCR and antimicrobial assay, however, A1, B1 and C1 showed more potent inhibitory activity than spiro compounds (A2, B2 and C2). On the other hand, as to C-5' substituents of pyrrolidine ring, the order of inhibitory activity was R = OH > R = OCH3 > R = H on Con A-induced proliferation of murine splenic lymphocytes assay. In MLCR and antimicrobial assay, however, the order of inhibitory activities were R = H > R = OCH3 > R = OH. Inhibitory activities of A4 which was lacked pyrrolidine ring were reduced on B16 melanoma cells adhesion assay and on cytotoxicity against tumor cells in vitro in comparison with those of A1.