Croatica Chemica Acta, Vol. 90 No. 4, 2017.
Original scientific paper
https://doi.org/10.5562/cca3273
Synthesis and In vitro Activity of N-sulfonylamidine-derived Pyrimidine Analogues
Luka Krstulović
; Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, HR-10000 Zagreb, Croatia
Dijana Saftić
; Laboratory for Biomolecular Interactions and Spectroscopy, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, HR-10000 Zagreb, Croatia
Hamit Ismaili
; Faculty of Mathematics and Natural Sciences, University of Pristina, Agim Ramadani n.n. 10000, Pristina, Kosovo
Miroslav Bajić
; Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, HR-10000 Zagreb, Croatia
Ljubica Glavaš-Obrovac
orcid.org/0000-0001-7497-296X
; Department of Medicinal Chemistry, Biochemistry and Laboratory Medicine, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Huttlerova 4, HR-31000 Osijek, Croatia
Biserka Žinić
orcid.org/0000-0002-1536-7142
; Laboratory for Biomolecular Interactions and Spectroscopy, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, HR-10000 Zagreb, Croatia
Abstract
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.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Keywords
pyrimidines; N-sulfonylamidines; multi-component synthesis; copper(I); in vitro
Hrčak ID:
198182
URI
Publication date:
29.12.2017.
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