Design and Synthesis of 4-substituted Quinazolines as Potent EGFR Inhibitors with Anti-breast Cancer Activity

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.

Cite this article as:

Ahmed F. Marwa*, Magdy Naja, Design and Synthesis of 4-substituted Quinazolines as Potent EGFR Inhibitors with Anti-breast Cancer Activity, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (6) . https://dx.doi.org/10.2174/1871520616666160923103222

DOI https://dx.doi.org/10.2174/1871520616666160923103222	Print ISSN 1871-5206
Publisher Name Bentham Science Publisher	Online ISSN 1875-5992