Antibiotics from basidiomycetes. XVII The effect of marasmic acid on nucleic acid metabolism.

Abstract
From submerged cultures of Lachnella villosa, Lachnella sp. 541 and Peniophora laeta, marasmic acid, a metabolite first described from surface cultures of Marasmius conigenus, was isolated. The sesquiterpenoid exhibited potent antimicrobial [bacteria, fungi] and cytotoxic properties. In cells of the ascitic form of Ehrlich [mouse] carcinoma, RNA and DNA syntheses were preferentially inhibited. Marasmic acid inhibited RNA synthesis in isolated nuclei, but did not interfere with the transport of nucleoside precursors into the cells. RNA polymerase II and capping enzyme (mRNA guanylyltransferase), 2 enzymes of nucleic acid metabolism, were markedly affected after preincubation with marasmic acid. Apparently, marasmic acid acts on nucleic acid syntheses by direct inhibition of some of the enzymes involved. This mode of action would also explain its mutagenic properties. The preparation and testing of 2 derivatives revealed that the .alpha.,.beta.-unsaturated aldehyde is essential for the antimicrobial and cytotoxic activity of marasmic acid.