Ghorab Mostafa M, Alsaid Mansour S, Soliman Aiten M, Al-Mishari Abdullah A
a Department of Pharmacognosy, College of Pharmacy , King Saud University , Riyadh , Saudi Arabia.
b Department of Drug Radiation Research , National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority , Cairo , Egypt.
J Enzyme Inhib Med Chem. 2018 Dec;33(1):67-73. doi: 10.1080/14756366.2017.1389922.
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 acetamide 5-19 were synthesised from the starting material 4-(2-mercapto-4-oxobenzo[g]quinazolin-3(4H)-yl) benzenesulfonamide 4, to be evaluated as dual EGFR/HER2 inhibitors. The target compounds 5-19, 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. Compounds 6, 8, 10, and 16 showed excellent EGFR inhibitory activity and were further selected for screening as dual EGFR/HER2 inhibitors. The four selected compounds showed IC ranging from 0.009 to 0.026 µM for EGFR and 0.021 to 0.069 µM for the HER2 enzyme. Compound 8 was found to be the most potent in this study with IC 0.009 and 0.021 µM for EGFR and HER2, respectively.
靶向表皮生长因子受体（EGFR）已被证明在治疗多种实体瘤方面具有益处。因此，从起始原料4-(2-巯基-4-氧代苯并[g]喹唑啉-3(4H)-基)苯磺酰胺4合成了一系列新型的2-(4-氧代-3-(4-氨磺酰基苯基)-3,4-二氢苯并[g]喹唑啉-2-基硫代)-N-取代乙酰胺5-19，以评估其作为EGFR/HER2双重抑制剂的活性。对目标化合物5-19针对A549肺癌细胞系的细胞毒性活性进行了筛选。测定了EGFR酶的抑制百分比，并与作为参考药物的厄洛替尼进行了比较。化合物6、8、10和16表现出优异的EGFR抑制活性，并被进一步选为EGFR/HER2双重抑制剂进行筛选。所选的四种化合物对EGFR的半数抑制浓度（IC）范围为0.009至0.026µM，对HER2酶的IC范围为0.021至0.069µM。在本研究中发现化合物8是最有效的，其对EGFR和HER2的IC分别为0.009和0.021µM。
