Di- and tri-substituted s-triazine derivatives: Synthesis, characterization, anticancer activity in human breast-cancer cell lines, and developmental toxicity in zebrafish embryos

Abstract

Here we report on a small library based on a 4-aminobenzonitile-s-triazine moiety. We used a straightforward orthogonal synthetic pathway to prepare di- and tri-substituted s-triazine derivatives, whose basic structure was modified. The newly synthesized compounds were fully characterized by ¹H NMR, ¹³C NMR and elemental analysis. They showed strong anticancer activity against two human breast cancer cell lines (MIDA-MB-231 and MCF-7), with IC₅₀ values less than 1 µM. These s-triazine compounds were generally more selective towards hormone receptor-positive breast cancer cell line MCF-7 than the triple negative MDA-MB-231 cell line. Zebrafish embryos were used to test the developmental toxicity of the target compounds in vivo. The phenotype of embryos treated with the derivatives resembled that of those treated with estrogen disruptors. This observation strongly supports the notion that that these compounds induce their anticancer activity in human breast cancer cells via targeting the estrogen and progesterone receptors.

Keywords: 4-aminobenzonitile-s-triazine; Anticancer activity; Di- trisubstituted s-triazine; Zebrafish embryos.