Synthesis and In vitro Activity of N-sulfonylamidine-derived Pyrimidine Analogues

• Published in: Croatica Chemica Acta Vol. 90; no. 4; p. 625
• Main Authors: Krstulović, Luka, Saftić, Dijana, Ismaili, Hamit, Bajić, Miroslav, Glavaš-Obrovac, Ljubica, Žinić, Biserka
• Format: Journal Article Paper
• Language: English
• Published: Croatica Chemica Acta 2017; Hrvatsko kemijsko društvo
• Subjects: Chemical research; copper(I); in vitro; multi-component synthesis; N-sulfonylamidines; Properties; Pyrimidines; Structure-activity relationships (Pharmacology); Testing
• ISSN: 0011-1643; 1334-417X
• DOI: 10.5562/cca3273

Two novel series of N-sulfonylamidino pyrimidine derivatives were synthesized via Cu-catalyzed three-component reaction of propargylated nucleobases with different benzenesulfonyl azides and amines. In this way 4-acetamido, 4-methyl and 4-carboxybenzenesulfonyl amidine products 15-26 in the uracil series and 4-acetamidobenzenesulfonyl amidine derivatives 27-29 in the cytosine series were prepared in 34-69% yields. Attempts to prepare N-sulfonylamidino cytosine derivatives in reaction with 4-methylbenzenesulfonyl azide were unsuccessful. The cytosine derivatives 32 and 33 were prepared from the N-sulfonylamidino uracil derivatives via the C4 triazole intermediates. The prepared N-sulfonylamidino pyrimidine derivatives 1-28 were tested for the antiproliferative activity on a panel of seven tumor cell lines of different histological origin (HeLa, Caco-2, NCI-H358, Raji, HuT78, K562, Jurkat) and on normal MDCK I cells. Most of the synthesized compounds showed antiproliferative activity on the tested cell lines. Keywords: pyrimidines, N-sulfonylamidines, multi-component synthesis, copper(I), in vitro.