Synthesis of 1,2,3-triazolyl sulfonamido-ribofuranoside conjugates

Sulfonamides represent an important class of molecules possessing diverse biological activities; they are powerfull antimicrobial drugs, carbonic anhydrase inhibitors, antithyroid agents, antitumour drugs, etc.1 Recently, we have reported the synthesis of a series of pyrimidine nucleic base derivatives possessing sulfonamide pharmacophore, which showed promising in vitro antitumor activity.2 These results directed our interest toward sulfonamido-ribofuranoside derivatives as new candidates for compounds with antitumor activity. We explored the known methods of copper-catalyzed 1,3-dipolar cycloaddition for the synthesis of 1,2,3-triazolyl carbohydrate conjugate A,2,3 which was transformed into sulfonamido-ribofuranoside conjugate B and reversed nucleoside conjugate C. The cytotoxicity of compounds were tested against normal cells (MDCK1), human leukemia and lymphoma (K562, Raji) cell lines by the MTT assay. Depending on the dose applied compounds showed moderate to high antiproliferative activity against a panel of hematological malignancies in vitro.We are currently synthesizing more complex molecules using those analogs as the building blocks References : 1. Supuran, A., Scozzafava, A., Casini, A., Med. Res. Rev. 2003, 23, 146–189. 2. (a) Žinić B., Žinić M., Krizmanić I., EP 0 877 022 B1 (Bulletin 1003/16; 16.04.2003). (b) Kašnar-Šamprec, J.; Ratkaj, I.; Mišković, K.; Pavlak, M.; Baus-Lončar, M.; Kraljević Pavelić, S.; Glavaš-Obrovac, Ljubica; Žinić, B. Investigational new drugs (2011) (on line). 3. Rostovtsev, V. V., Green, L. G., Fokin, V. V.,Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 2596-2599. Hotha, S., Kashyap, S. .J. Org. Chem. 2006, 71, 364–367