Twenty new quinazolinone derivatives bearing a piperonyl moiety were designed and synthesized. The structures of the target compounds were in agreement with the microanalytical and spectral data. Compounds 4-10, 13, 14 and 17-27 were screened for their cytotoxic activity against HepG-2 and MCF-7 cancer cell lines. The target compounds showed IC₅₀ in the range of 2.46–36.85 µM and 3.87–88.93 µM for HepG-2 and MCF-7, respectively. The promising compounds 7, 19, 26 and 27 were selected to measure their EGFR inhibitory activity. The IC₅₀ values of the promising compounds were in the range of 146.9–1032.7 nM for EGFR in reference to Erlotinib (IC₅₀ = 96.6 nM). In further studies on compounds 7, 19, 26 and 27 using HepG-2 cell line, there was significant overexpression of p21 and downregulation of two members of IAPs protein family; Survivin and XIAP, relative to their controls. Annexin V-FITC and caspase-3 analyses have established a significant increase in early apoptosis. Moreover, the four selected compounds have impaired cell proliferation by cell cycle arrest at the G2/M phase compared to their respective control. Considering radiotherapy as the primary treatment for many types of solid tumors, the radiosensitizing abilities of compounds 7, 19, 26 and 27 were measured against HepG-2 and MCF-7 cell lines combined with a single dose of 8 Gy gamma radiation. Measurement of the IC₅₀ of the promising compounds after irradiation revealed their ability to sensitize the cells to the lethal effect of gamma irradiation (IC₅₀ = 1.56–4.32 µM and 3.06–5.93 µM for HepG-2 and MCF-7 cells, respectively). Molecular docking was performed to gain insights into the ligand-binding interactions of 7, 19, 26 and 27 inside the EGFR binding sites and revealed their essential interactions, explaining their good activity towards EGFR.

设计并合成了 20 种带有胡椒基部分的新型喹唑啉酮衍生物。目标化合物的结构与微量分析和光谱数据一致。化合物4 - 10，13，14和17 - 27筛选了对人肝癌HepG-2和MCF-7癌细胞系的细胞毒活性。目标化合物对 HepG-2 和 MCF-7 的IC _{50 分别}在 2.46–36.85 µM 和 3.87–88.93 µM 范围内。选择有前景的化合物7、19、26和27来测量它们的 EGFR 抑制活性。IC ₅₀相对于厄洛替尼 (IC ₅₀  = 96.6 nM) ，有希望的化合物的 EGFR 值在 146.9–1032.7 nM 的范围内。在化合物进一步研究7，19，26和27使用肝癌HepG-2细胞系，有p21和IAP的蛋白家族的两个成员的下调的表达显著; Survivin 和 XIAP，相对于它们的对照。Annexin V-FITC 和 caspase-3 分析表明早期细胞​​凋亡显着增加。此外，与它们各自的对照相比，这四种选定的化合物由于细胞周期停滞在 G2/M 期而削弱了细胞增殖。考虑放疗作为主要治疗对于许多类型的实体瘤，化合物的放射增敏能力7，19，26和27项针对 HepG-2 和 MCF-7 细胞系与单剂量 8 Gy 伽马辐射相结合进行了测量。辐照后有希望的化合物的 IC ₅₀的测量表明它们能够使细胞对伽马辐射的致死效应敏感（ 对于 HepG-2 和 MCF-7 细胞，IC _{50 分别}为 1.56–4.32 µM 和 3.06–5.93 µM） . 分子对接进行从中深入了解的配体结合相互作用7，19，26和27的EGFR结合位点内，并透露其基本相互作用，对解释他们的EGFR良好的活性。