Benzo[g]quinazolin-based scaffold derivatives as dual EGFR/HER2 inhibitors. (1st January 2018)

• Record Type: Journal Article
• Authors: Ghorab, Mostafa M.; Alsaid, Mansour S.; Soliman, Aiten M.; Al-Mishari, Abdullah A.
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 33:Number 1(2018)
• Page Start: 67
• Page End: 73
• Publication Date: 2018-01-01
• Subjects: Benzo[g]quinazolin -- benzenesulfonamide -- EGFR -- HER2; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2017.1389922
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: Targeting EGFR has proven to be beneficial in the treatment of several types of solid tumours. So, a series of novel 2-(4-oxo-3-(4-sulfamoylphenyl)-3, 4-dihydrobenzo[g]quinazolin-2-ylthio)- N -substituted acetamide5 –19 were synthesised from the starting material 4-(2-mercapto-4-oxobenzo[g]quinazolin-3(4 H )-yl) benzenesulfonamide4, to be evaluated as dual EGFR/HER2 inhibitors. The target compounds5 –19, were screened for their cytotoxic activity against A549 lung cancer cell line. The percentage inhibition of EGFR enzyme was measured and compared with erlotinib as the reference drug. Compounds6, 8, 10, and16 showed excellent EGFR inhibitory activity and were further selected for screening as dual EGFR/HER2 inhibitors. The four selected compounds showed IC50 ranging from 0.009 to 0.026 µM for EGFR and 0.021 to 0.069 µM for the HER2 enzyme. Compound8 was found to be the most potent in this study with IC50 0.009 and 0.021 µM for EGFR and HER2, respectively. Graphical Abstract: