کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1359750 | 981412 | 2009 | 15 صفحه PDF | دانلود رایگان |
The synthesis of some novel azasteroids and thiasteroids based on a pregnan nucleus with a Δ7 double bond in two to five steps from the key aldehyde (3S,20S)-20-formylpregn-7-en-3-yl acetate has been disclosed herein. These compounds were evaluated as potential inhibitors of the enzyme Δ24-sterol methyltransferase (24-SMT), which is a key enzyme in the biosynthesis of ergosterol, and for their effects on the growth of the yeast Yarrowia lipolytica. Most of the side chain modified analogues were recognized as 24-SMT inhibitors, and in particular the 23-azasteroids 5f–5i and the 24-azasteroid 11 showed potent antifungal activity. The target enzyme could be identified unambiguously using an improved whole-cell assay combined with GC–MS analysis of the sterol pattern resulting upon incubation with the inhibitors.
Novel antifungal Δ7-azasteroids and thiasteroids were prepared as inhibitors of the enzyme Δ24-sterol methyltransferase (24-SMT).Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 17, Issue 23, 1 December 2009, Pages 8123–8137