This article shows the structures of the lipid-soluble thiamine prodrugs, and the cyclization reactions that have to occur to form thiamine from these drugs, in vivo, look problematic to me:
http://ecam.oxfordjournals.org/cgi/content/full/3/1/49 (pubmed: http://www.ncbi.nlm.nih.gov/pubmed/16550223?dopt=Abstract) (Lonsdale, 2006)
Those drugs look just really reactive. What's the fate of the S-benzoyl- moiety of S-benzoylthiamine derivatives, such as benfotiamine? That seems like it would be an issue. I've read that thiamine can serve as an antioxidant, to a certain extent, and that oxidized thiamine derivatives can form adducts with intracellular proteins. But presumably there would be some immunological tolerance to those modified proteins.
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