The synthesis and biological evaluation of novel guanidino sugars as isonucleoside analogs is described. 5-Guanidino xylofuranoses containing 3-O-saturated/unsaturated hydrocarbon or aromatic-containing moieties were accessed from 5-azido xylofuranoses via reduction followed by guanidinylation with N,N'-bis(tert-butoxycarbonyl)-N''-triflylguanidine. Molecules comprising novel types of isonucleosidic structures including 5-guanidino 3-O-methyl-branched N-benzyltriazole isonucleosides and a guanidinomethyltriazole 3'-O-dodecyl xylofuranos-5'-yl isonucleoside were accessed. The guanidinomethyltriazole derivative and a 3-O-dodecyl (N-Boc)guanidino xylofuranose were revealed as selective inhibitors of acetylcholinesterase (Ki =22.87 and 7.49 μM, respectively). The latter also showed moderate antiproliferative effects in chronic myeloid leukemia (K562) and breast cancer (MCF-7) cells. An aminomethyltriazole 5'-isonucleoside was the most potent molecule with low micromolar GI50 values in both cells (GI50 =6.33 μM, 8.45 μM), similar to that of the drug 5-fluorouracil in MCF-7 cells. Moreover, the most bioactive compounds showed low toxicity in human fibroblasts, further indicating their interest as promising lead molecules.

• MeSH
• Acetylcholinesterase MeSH
• Humans MeSH
• MCF-7 Cells MeSH
• Molecular Structure MeSH
• Breast Neoplasms * MeSH
• Antineoplastic Agents * chemistry   MeSH
• Structure-Activity Relationship MeSH
• Xylose chemistry   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH