Abstract
Three novel pyrazolo-[4,3-e][1,2,4]triazolopyrimidine derivatives (1, 2, and 3) were designed, synthesized, and evaluated for their in vitro biological activity. All three compounds exhibited different levels of cytotoxicity against cervical and breast cancer cell lines. However, compound 1 showed the best antiproliferative activity against all tested tumor cell lines, including HCC1937 and HeLa cells, which express high levels of wild-type epidermal growth factor receptor (EGFR). Western blot analyses demonstrated that compound 1 inhibited the activation of EGFR, protein kinase B (Akt), and extracellular signal-regulated kinase (Erk)1/2 in breast and cervical cancer cells at concentrations of 7 and 11 µM, respectively. The results from docking experiments with EGFR suggested the binding of compound 1 at the ATP binding site of EGFR. Furthermore, the crystal structure of compound 3 (7-(4-bromophenyl)-9-(pyridin-4-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine) was determined by single crystal X-ray analysis. Our work represents a promising starting point for the development of a new series of compounds targeting EGFR.
Highlights
Introduction distributed under the terms andCancer ranks in the top two of diseases with the highest death toll, and accounts for 13% of total deaths worldwide [1]
In a continuation of these efforts, we report the design, synthesis, and bioassay for pyrazolo-[4,3e][1,2,4]triazolopyrimidine [1,2,3] and the crystal structure of 7-(4-bromophenyl)-9-(pyridin4-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine [3]
IR spectra revealed the existence of a CN group about 2230 cm−1 as it is appeared in the reactant (V), while the absence of NH2 band was recorded, which appears in the starting materials (V) around 3300–3100 cm−1, as well as the appearance of the vibrational band of
Summary
Associated Member of Faculty of Science, Tuebingen University, Auf der Morgenstelle 8, 72076 Tübingen, Germany. Academic Editors: Youping Deng, Yuanyuan Fu, Fan Zhang, Mehdi Pirooznia and Filippo Minutolo. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil-
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