Design and Synthesis of 4-substituted Quinazolines as Potent EGFR Inhibitors with Anti-breast Cancer Activity.
BACKGROUND
Cancer is a major health problem to human beings around the world. Many quinazoline derivatives were reported to have potent cytotoxic activity.


OBJECTIVE
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.


METHODS
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).


RESULTS
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.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo, Egypt.
Marwa F
MF
Ahmed
Department of Pharmacology and toxicology, Faculty of Pharmacy, Taif University, Taif 26571, Saudi Arabia.
Naja
N
Magdy
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors
Breast cancer; EGFR TK; IC50; design; quinazolines; synthesis