Fifteen new quinazolinone derivatives bearing benzenesulfonamide moiety with variable acetamide tail were synthesized. The structures assigned to the products were concordant with the microanalytical and spectral data. Compounds 4–18 were screened for their ability to induce the antioxidant enzyme NAD(P)H: quinone oxidoreductase 1 (NQO1) in cells, a classical target for transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). The 2-((6,8-diiodo-4-oxo-3-(4-sulfamoylphenyl)-3,4-dihydroquinazolin-2-yl)thio)-N-(3,4,5-trimethoxyphenyl) acetamide 15 showed the most potent NQO1 inducer activity in vitro. Compound 15 had low toxicity in mice (LD₅₀ = 500 mg/kg). It also reduced the damaging effects of gamma radiation, as assessed by the levels of Nrf2, NQO1, reactive oxygen species (ROS) and malondialdehyde (MDA) in liver tissues. In addition, compound 15 showed amelioration in the complete blood count of irradiated mice and enhanced survival over a period of 30 days following irradiation. Molecular docking of 15 inside the Nrf2-binding site of Kelch-like ECH associated protein 1 (Keap1), the main negative regulator of Nrf2, showed the same binding interactions as that of the co-crystallized ligand considering the binding possibilities and energy scores. These findings suggest that compound 15 could be considered as a promising antioxidant and radiomodulatory agent.

合成了十五个带有可变乙酰胺尾基的带有苯磺酰胺部分的新喹唑啉酮衍生物。分配给产物的结构与显微分析和光谱数据一致。筛选了化合物4-18诱导细胞中抗氧化酶NAD（P）H：醌氧化还原酶1（NQO1）的能力，这是转录因子核因子红系2相关因子2（Nrf2）的经典靶标。的2 - （（6,8-二碘-4-氧代-3-（4-氨磺酰苯基）-3,4-二氢喹唑啉-2-基）硫基） - ñ - （3,4,5-三甲氧基苯基）乙酰胺15显示NQO1最强的体外诱导活性。化合物15对小鼠的毒性低（LD ₅₀ = 500 mg / kg）。如肝脏组织中Nrf2，NQO1，活性氧（ROS）和丙二醛（MDA）的水平所评估，它还减少了伽马射线的破坏作用。另外，化合物15在辐照的小鼠的全血细胞计数中显示出改善，并且在辐照后的30天内增加了存活率。考虑到结合的可能性和能量得分，在Nrf2的主要负调控因子Kelch-like ECH相关蛋白1（Keap1）的Nrf2结合位点内部有15个分子对接，显示出与共结晶配体相同的结合相互作用。这些发现表明化合物15可以被认为是有前途的抗氧化剂和放射调节剂。