Marwa F. Ahmed* and Radwan El-Haggar Pages 1563 - 1569 ( 7 )
Background: Cancer is one of the most dangerous diseases with quite a high mortality rate. Many quinazoline derivatives show potent anticancer activity.
Objective: In this work our aim is to develop novel, safe and effective anticancer agents.
Method: New 6,8-dibromo-2-(4-chlorophenyl)-quinazoline-sulphonamide hybrids and some Schiff´s base analogs were synthesized, and their structures were confirmed by spectral and elemental analysis. Cytotoxicity of all synthesized compounds was evaluated on three cancer cell lines MCF7, HCT116 and HEPG2 using sulpharodamine- B assay method and doxorubicin as a reference drug. All tested compounds show promising cytotoxic activities on the three cell lines.
Results: Compound IXd was 2 times more active than doxorubicin on MCF7 cancer cells, while it was 3 times more potent than doxorubicin on HCT116 cancer cells. Compound IV was 2 times more active than doxorubicin while compound VI exhibited similar activity to doxorubicin on HEPG2 cell line. The most active compounds were tested against epidermal growth factor receptor tyrosine kinase (EGFR TK). Compounds IV, IXd, IXf show the most potent inhibitory percent 62.3, 91.1, 91.6 respectively. Compounds IV, V, VII, IXd, IXf caused a significant increase of CASP3 activity with range 86.5-37.6 %.
Conclusion: The present work led to the discovery of new cytotoxic compounds having quinazoline pharmacophore.
Quinazolinone-sulphonamide hybrids, schiff´s base, antitumor, tyrosine kinases, analogs, cytotoxic activity.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo