Design and Synthesis of 4-Anilinothieno[2,3-d]pyrimidine-Based Compounds as Dual EGFR/HER-2 Inhibitors
Abd El Hadi, Soha R; Lasheen, Deena S.; Hassan, Mahmoud A; Khaled A M Abouzid;
Abstract
Dual inhibition of the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor 2 (HER-2) is an attractive cancer therapeutic approach. In this study, new series of 4-anilinothieno[2,3-d]pyrimidines were designed, synthesized, and tested as dual EGFR/HER-2 kinase inhibitors. Five compounds (8a, 8b, 8e-g) demonstrated low to submicromolar inhibition of both kinases with IC50 values of 1.2, 0.6, 0.3, 0.2, 0.4 μM and 8.2, 3.4, 1.3, 0.5, 2.7 μM for the EGFR and HER-2, respectively. Introduction of a 5,6-tetramethylene moiety into the thienopyrimidine core bearing a 4-(3-fluorobenzyloxy)-3-chloroaniline tail resulted in a favorable increase in both the EGFR and HER-2 inhibitory activities. Compound 8f (IC50 EGFR/HER-2: 0.2/0.5 μM) also exhibited significant cell growth inhibition on some specific NCI cell lines, especially ovarian, breast, non-small-cell lung cancer, and renal cancer cell lines.
Other data
Title | Design and Synthesis of 4-Anilinothieno[2,3-d]pyrimidine-Based Compounds as Dual EGFR/HER-2 Inhibitors | Authors | Abd El Hadi, Soha R; Lasheen, Deena S. ; Hassan, Mahmoud A; Khaled A M Abouzid | Keywords | Antiproliferative activity;Docking study;EGFR/HER2 kinase;Thienopyrimidine | Issue Date | Nov-2016 | Publisher | WILEY-V C H VERLAG GMBH | Journal | Archiv der Pharmazie | Volume | 349 | Issue | 11 | Start page | 827 | End page | 847 | ISSN | 0365-6233 | DOI | 10.1002/ardp.201600197 | PubMed ID | 27734525 | Scopus ID | 2-s2.0-84991085129 | Web of science ID | WOS:000388276100002 |
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