N-acetyl-D-mannosamine analogues as potential inhibitors of sialic acid biosynthesis.
The 1,3,6-tri-O-acetyl and 1,3,6-tri-O-acetyl-4-O-mesyl analogues of N-acetyl-D-mannosamine and the corresponding N-trifluoroacetyl derivative have been synthesized, and their effects on the proliferation of Friend erythroleukemia cells in culture have been evaluated. The acetamido series showed a dependency on the 4-substituent for optimum cytotoxicity while the trifluoroacetamido series did not. Thus, the 1,3,4,6-tetra-O-acetyl and 1,3,6-tri-O-acetyl-4-O-mesyl analogues of N-acetyl-D-mannosamine were 10-fold and 42-fold more active, respectively, than 2-acetamido-1,3,6-tri-O-acetyl-2-deoxy-alpha-D-mannopyranose as inhibitors of cellular replication. The corresponding trifluoroacetamido analogues were essentially equiactive and had a potency equivalent to that of the 4-O-mesyl derivative in the acetamido series.
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006595:Hexosamines / Q000138:chemical synthesis / Q000494:pharmacology*; D004915:Leukemia, Erythroblastic, Acute; D007942:Leukemia, Experimental; D051379:Mice; D012794:Sialic Acids / Q000096:biosynthesis*
D006595:Hexosamines; D012794:Sialic Acids