Manumycin A and Its Analogues Are Irreversible Inhibitors of Neutral Sphingomyelinase

Abstract

Valuable tools for experimental anti-inflammatory therapy and for clarifying the biological role of neutral sphingomyelinase and ceramide might be represented by manumycins. The antibiotic manumycin A (1), known as a Ras farnesyltransferase inhibitor, and some of its analogues were identified as irreversible inhibitors of neutral sphingomyelinase. The simple analogue 2 is readily accessible, stable and hitherto represents the most potent irreversible inhibitor of neutral sphingomyelinase.