Ghorab Mostafa M, Soliman Aiten M, Habieb Mahmoud E, Abdou Fatma Y
Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo 11787, Egypt..
Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo 11787, Egypt.
Bioorg Chem. 2025 Jun 15;160:108439. doi: 10.1016/j.bioorg.2025.108439. Epub 2025 Apr 3.
With the increased use of radiation in cancer therapy, new effective antioxidants and anti-inflammatory agents are required to alleviate the negative impact caused by irradiation. A set of novel N-substituted-2-((2-oxo-2-((4-sulfamoylphenyl)amino)ethyl)thio) acetamide derivatives 3-14 was synthesized to act as possible radiation mitigators. The synthesized compounds were screened for their anti-inflammatory and antioxidant potential using selective COX-2 inhibitory activity and DPPH assays compared to celecoxib and ascorbic acid, respectively. Compound 9 was the most active in this series with selective COX-2 inhibitory activity (IC = 0.373 μM), and free radical scavenging properties (IC = 4.89 μM). In vitro and in vivo studies demonstrated that compound 9 exhibited a high safety profile, with low cytotoxicity on normal cells (IC > 800 μM) and a median lethal dose (LD) of 300 mg/kg. The potential renal radiomodulatory effect of the promising candidate was investigated in mice exposed to gamma radiation (6 Gy). Compound 9 successfully reduced radiation-induced oxidative stress, as seen by lower levels of reactive oxygen species (ROS), malondialdehyde (MDA), and enhancement in the levels of reduced Glutathione (GSH) in kidney tissues. Moreover, compound 9 reduced kidney inflammatory markers; Nuclear factor kappa B (NF-κB) and Interleukin 6 (IL-6) in irradiated mice, while lowering serum urea and creatinine levels relative to untreated irradiated group. Compound 9 additionally modified the histological alterations caused by gamma irradiation-induced tubular epithelial cell necrosis. Accordingly, compound 9 can help to reduce the adverse effects of irradiation.
随着放射疗法在癌症治疗中的应用增加，需要新的有效抗氧化剂和抗炎剂来减轻辐射造成的负面影响。合成了一组新型的N-取代-2-((2-氧代-2-((4-氨磺酰基苯基)氨基)乙基)硫代)乙酰胺衍生物3-14，作为可能的辐射缓解剂。分别与塞来昔布和抗坏血酸相比，使用选择性COX-2抑制活性和DPPH测定法对合成的化合物进行抗炎和抗氧化潜力筛选。化合物9在该系列中活性最高，具有选择性COX-2抑制活性（IC = 0.373 μM）和自由基清除特性（IC = 4.89 μM）。体外和体内研究表明，化合物9具有高安全性，对正常细胞的细胞毒性低（IC > 800 μM），半数致死剂量（LD）为300 mg/kg。在接受γ辐射（6 Gy）的小鼠中研究了该有前景候选物的潜在肾脏辐射调节作用。如肾脏组织中活性氧（ROS）、丙二醛（MDA）水平降低以及还原型谷胱甘肽（GSH）水平升高所示，化合物9成功降低了辐射诱导的氧化应激。此外，化合物9降低了肾脏炎症标志物；辐照小鼠中的核因子κB（NF-κB）和白细胞介素6（IL-6），同时相对于未治疗的辐照组降低了血清尿素和肌酐水平。化合物9还改善了γ辐射诱导的肾小管上皮细胞坏死引起的组织学改变。因此，化合物9有助于减少辐射的不良影响。
