Studies on a new antibiotic M-92 produced by Micromonospora. III. Biological activities

The six major components of M-92, a new antibiotic complex produced by Micromonospora verruculosa MCRL 0404 showed a similar type of antimicrobial spectrum. Among these components, VA-2 exhibited the most potent antimicrobial activity, particularly significantly against some Gram-positive bacteria and Neisseria. VA-2 and BN-1 also exhibited marked inhibitory effects against L-forms of Staphylococcus aureus 209P and Mycoplasma. The MICs of VA-2, BA-4 and BN-1 were remarkably affected by the pH of the test medium, the inoculum size and the amount of horse serum added in the medium. By intraperitoneal administration, these components showed good protective effects in mice infected intraperitoneally with Staphylococcus aureus Smith. However, the protective effect decreased remarkably by other administration routes. In addition, components such as VA-2 and BN-1 exhibited cytotoxicity against HeLa S-3 cells in vitro and excellent in vivo antitumor activity against Ehrlich carcinoma. VA-2 possessed a high order of acute toxicity to mice [LD50:1.9 mg/kg (i.p.); 1.8 mg/kg (i.v.)], but others were relatively less toxic.