ISOLATION, CHARACTERIZATION AND BIOLOGICAL-ACTIVITIES OF CONCANAMYCINS AS INHIBITORS OF LYSOSOMAL ACIDIFICATION

Four new analogues of concanamycin family, designated concanamycins D, E, F and G, were isolated from the mycelium of Streptomyces sp. A1509 by solvent extraction, silica gel column chromatography and HPLC. Structures of these compounds were identified by the combination of spectroscopic analyses. All of these compounds were structurally related to concanamycins A, B and C, which had been isolated previously, and inhibited the acidification of rat liver lysosomes at 10(-11) approximately 10(-9)M concentration. The structure-activity study showed that the 18-membered macrolide ring and the 6-membered hemiketal ring portions of the molecules of concanamycin family are responsible for potent inhibitory activity.