1,2,3-Triazole-containing flex-nucleoside analogs and sulfonamido-ribofuranoside conjugates: design, synthesis, and antiproliferative potential

• Published in: New journal of chemistry 2023-09, Vol.47 (37), p.17434-17448
• Main Authors: Safti, Dijana Pavlovi, Ban, eljka, Špoljari, Katarina Miškovi, Glavaš-Obrovac, Ljubica, ini, Biserka
• Format: Article
• Language: English
• Subjects: Alkynes; Antiproliferatives; Chemical reactions; Chemical synthesis; Conjugates; Coupling (molecular); Halides; Ribose; Sodium azides; Sugar; Sulfonamides; Triazoles; Tumors; Uracil
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/d3nj03724j

The design and synthesis of new C 5-[1,2,3]triazolyl-uracil/uridine fleximers and 1,2,3-triazolyl-sulfonamido-ribofuranoside conjugates useful as versatile building blocks for the preparation of more complex molecules is described. In order to prepare C 5-triazolyl-pyrimidine derivatives, starting 5-ethynyl-uracil/uridine derivatives were synthesized using Sonogashira coupling, and the azides were generated in situ from alkyl halides and NaN 3 , or 5-azido sugars were used. CuAAC click reactions were performed under classical conditions, and C 5-triazolyl-uracil/uridine derivatives were prepared in good yields. Two synthetic routes were used to prepare 1,4-disubstituted 1,2,3-triazolyl-sulfonamido-ribofuranoside conjugates. The first 1,2,3-triazolyl-ribofuranoside conjugate, where a 1,2,3-triazole ring links two ribose, was synthesized by click reactions and then converted into sulfonamido-ribofuranoside conjugates using commercially available sulfonamides. However, the sulfonamidoglycosidation reactions gave the desired products in low yields. In the second route, 5-azido-ribosyl-sulfonamides were synthesized, which were then subjected to a click reaction in a microwave reactor with a terminal sugar alkyne, giving the desired 1,4-disubstituted 1,2,3-triazolyl sulfonamido-ribofuranoside conjugates in excellent yields. Novel compounds were evaluated for their antiproliferative effects on six selected tumors and one normal cell line. The investigated compounds influenced tumor cell growth differently depending on the cell line, and the dose applied. The design and synthesis of new C 5-[1,2,3]triazolyl-uracil/uridine fleximers and 1,2,3-triazolyl-sulfonamido-ribofuranoside conjugates useful as versatile building blocks for the preparation of more complex molecules is described.