Concanamycin A

Concanamycin A, a macrolide antibiotic, derived from S.diastatochromogenes is an cytotoxic compound which inhibits acidification of organelles and perforin-mediated cytotoxicity. It is effective against several fungi and yeasts. Concanamycin A is an exceptionally potent and specific inhibitor of the ATP-driven proton pumps known as vacuolar type H+-ATPases (V-ATPases). V-ATPases acidify intracellular compartments and translocate protons across the plasma membrane. Intracellular V-ATPases play an important role in endocytosis and intracellular membrane trafficking, while plasma membrane V-ATPases are important in processes such as urinary acidification and bone resorption. Treatment of murine cells with Concanamycin A results in apoptosis, evidenced by an increase in fragmented DNA and the number of apoptotic cells with hypodiploid DNA. Concanamycin A induced production of nitric oxide and decreased cell growth and survival in mouse leukemic monocyte cells.