Title:Design and Synthesis of 4-substituted Quinazolines as Potent EGFR Inhibitors with Anti-breast Cancer Activity
Volume: 17
Issue: 6
Author(s): Marwa F. Ahmed*Naja Magdy
Affiliation:
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo,Egypt
Keywords:
Breast cancer, EGFR TK, IC50, quinazolines, synthesis, design.
Abstract: Background: Cancer is a major health problem to human beings around the world. Many quinazoline
derivatives were reported to have potent cytotoxic activity.
Aims: Our aim in this work is the discovery of potent epidermal growth factor receptor (EGFR) inhibitors with
anti-breast cancer activity containing 4-substituted quinazoline pharmacophore.
Method: Novel series of 4-substituted 6,8-dibromo-2-(4-chlorophenyl)-quinazoline derivatives have been
designed and synthesized. New derivatives were tested against MCF-7 (human breast carcinoma cell line) and
screened for their inhibition activity against epidermal growth factor receptor tyrosine kinase (EGFR-TK).
Result: Most of the tested compounds show potent antiproliferative activity and EGFR-TK inhibitory activity.
Compounds VIIIc and VIIIb exerted powerful cytotoxic activity (IC50 3.1 and 6.3 μM) with potent inhibitory
percent (91.1 and 88.4%) against EGFR-TK. Compounds IX, VIIa, X, VIIb, VIc, V, IV, VIa and VIb showed
promising cytotoxic effects with IC50 range (12-79 μM) with good activity against EGFR-TK with the inhibitory
percent (85.4-60.8%). On the other hand, compounds VIIc, VIIIa exerted low cytotoxic effects as revealed from
their IC50 value (124 and 144 μM) with low activity against EGFR-TK with inhibitory percent 30.6 and 29.1%
respectively.
