Leuseramycin

A new antibiotic leuseramycin has been isolated from the cultured mycelium of the strain of Streptomyces hygroscopicus TM-531. Physicochemical data, in particular those of 1H- and 13C-NMR spectra, revealed that leuseramycin is closely related to dianemycin in its structure, the former having a methyl group in place of the hydroxymethyl group at C-30. It is active against Gram-positive bacteria, some phytopathogenic fungi and some protozoa.

We examined the effect of various polyether antibiotics on colchicine resistance in multidrug-resistant KB-C4 cells which exhibit about 4,000-fold resistance to colchicine. As a result, 4 out of 14 polyether antibiotics were found to reverse colchicine resistance. Among them, laidlomycin was the most potent. It potentiated colchicine cytotoxicity on KB-C4 cells about 700-fold at 1 microgram/ml. Degree of potentiation was calculated by dividing of the IC50 value of colchicine in the absence of a polyether antibiotic by the IC50 value of colchicine in the presence of the polyether antibiotic. Monensin, dianemycin, and leuseramycin at 3 micrograms/ml also potentiated the cytotoxicity, about 100-fold. We previously reported that inostamycin is a potent chemosensitizer in KB-C4 cells. Although lysocellin has a structure very similar to that of inostamycin, it didn't reverse colchicine resistance. It slightly increased [3H]vinblastine accumulation in KB-C4 cells and weakly inhibited the [3H]vinblastine binding to KB-C4 plasma membranes.