| Autor: |
Aliwaini S; Department of Biology and Biotechnology, Islamic University of Gaza, Gaza P.O. Box 108, Palestine., Abu Thaher B; Chemistry Department, Faculty of Science, Islamic University of Gaza, Gaza P.O. Box 108, Palestine., Al-Masri I; Faculty of Pharmacy, Al-Azhar University, Gaza P.O. Box 1277, Palestine., Shurrab N; Chemistry Department, Al Azhar University-Gaza, Gaza P.O. Box 1277, Palestine., El-Kurdi S; Chemistry Department, Faculty of Science, Islamic University of Gaza, Gaza P.O. Box 108, Palestine., Schollmeyer D; Department of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55099 Mainz, Germany., Qeshta B; Chemistry Department, Faculty of Science, Islamic University of Gaza, Gaza P.O. Box 108, Palestine., Ghunaim M; Department of Biology and Biotechnology, Islamic University of Gaza, Gaza P.O. Box 108, Palestine., Csuk R; Department of Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 2, 06120 Halle, Germany., Laufer S; Department of Pharmaceutical Chemistry, Pharmaceutical Institute, University of Tuebingen, Auf der Morgenstelle 8, 72076 Tuebingen, Germany., Kaiser L; Institute of Precision Medicine, Faculty of Medical and Life Sciences, Furtwangen University (HFU), Jakob-Kienzle-Strasse 17, 78054 Villingen-Schwenningen, Germany.; Institute of Pharmaceutical Sciences, University of Freiburg, Albertstraße 25, 79104 Freiburg, Germany., Deigner HP; Institute of Precision Medicine, Faculty of Medical and Life Sciences, Furtwangen University (HFU), Jakob-Kienzle-Strasse 17, 78054 Villingen-Schwenningen, Germany.; EXIM Department, Fraunhofer Institute IZI Leipzig, Schillingallee 68, 18057 Rostock, Germany.; Associated Member of Faculty of Science, Tuebingen University, Auf der Morgenstelle 8, 72076 Tübingen, Germany. |
| Abstrakt: |
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)-7 H -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. |
