Mode of action of the azasteroid antibiotic 15-aza-24 methylene-d-homocholesta-8,14-dien-3 beta-ol in Ustilago maydis.
Ustilago maydis sporidia treated with 0.1 mug of azasterol (15-aza-24-methylene-d-homocholesta-8,14-dien-3beta-ol) per ml appeared branched and vacuolated after 6 h of incubation. Sporidial multiplication, dry weight increase, and synthesis of protein, deoxyribonucleic acid, and ribonucleic acid were only slightly or moderately inhibited during the initial 3 h of incubation. An increase of free fatty acids was observed in lipid extracts of treated sporidia after incubation for 3 h or more. Ergosterol synthesis was completely inhibited within 1 h and there was a gradual decline of ergosterol content during 6 h which was accompanied by an accumulation of the sterol intermediate ergosta-8,14-dien-3beta-ol. The results indicate that toxicity of the azasterol results from specific inhibition of the reduction of the sterol C-14(15) double bond. A triarimol-tolerant strain of Cladosporium cucumerinum was tolerant to the azasterol, but an imazalil-tolerant strain of Aspergillus nidulans was not.
D000935:Antifungal Agents / Q000494:pharmacology*; D001233:Aspergillus nidulans / Q000187:drug effects; D001378:Azasteroids / Q000378:metabolism / Q000494:pharmacology*; D001487:Basidiomycota / Q000187:drug effects*; D002775:Cholestadienols / Q000494:pharmacology; D002963:Cladosporium / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004875:Ergosterol / Q000096:biosynthesis*; D005656:Fungal Proteins / Q000096:biosynthesis; D012313:RNA / Q000096:biosynthesis; D013260:Steroids, Heterocyclic / Q000494:pharmacology*; D013261:Sterols / Q000096:biosynthesis; D014588:Ustilago / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
D000935:Antifungal Agents; D001378:Azasteroids; D002775:Cholestadienols; D005656:Fungal Proteins; D013260:Steroids, Heterocyclic; D013261:Sterols; D012313:RNA; D004247:DNA; D004875:Ergosterol