Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Two series of new 1,2,3-triazole-purine hybrids were synthesized in considerable yields (up to 87%), starting from benzyl azides and purine alkynes, via 1,3-dipolar cycloaddition reaction catalyzed with Cu(I). The first (
7a
-
k)
and second (
8a
-
k)
series of hybrids employed kinetin and adenine as precursors, respectively. All synthesized compounds were evaluated in vitro for their antiproliferative activity against two breast cancer cell lines (MCF-7 and MDA-MB-231) and a non-tumor cell line (MCF-10A) to estimate their selectivity. From the twenty-two synthesized compounds, eight (
4, 7a
-
e
,
7
h
and
8a)
were active against both tumor cell lines, especially the kinetin derivatives, which displayed better results than the adenine derivatives. The original kinetin molecule was not active, suggesting that structural changes in its derivatives were favorable to induce cytotoxic effects in the tested cells. Compounds
7c
and
7d
were the most active, with IC
50
of 22.3 µM and 22.9 µM for MCF-7, and IC
50
of 9.3 µM and 16.7 µM for MDA-MB-231, respectively. In addition, the ADMET in silico study indicated that the active compounds (
4, 7a
-
e
,
7
h
and
8a)
presented drug-like similarities and a potential use as anticancer agents.
Graphical Abstract