Abstract：
New 4-nitrobenzyl derivatives were designed and synthesised by nucleophilic substitution reactions of 4-nitrobenzyl bromide with malonic acid and its derivatives. The synthesised molecules were characterised using mass analysis and spectroscopic techniques and tested for their antioxidant properties using various methods, such as nitric oxide, DPPH, and hydrogen peroxide radical scavenging methods. The anti-inflammatory activities of the molecules were assessed using RBC membrane stabilisation and albumin denaturation methods. We evaluated the compounds\' potential anti-prostate cancer activity using the DU145 cell line. The MTT assay determined the cell viability, indicating good anti-proliferative activity. The molecule 3c exhibited the highest potency, with a CTC50 of 11.83 µg/mL. Molecular dynamics simulations were performed to study the stability of the ligand within the protein after docking and the resulting protein-ligand complex. The in vivo analysis of molecule 3c in the DAL xenograft model demonstrated promising results. The increase in life span, reduction in tumor volume, and comparable effects to standard drugs are encouraging features that suggest that molecule 3c may possess significant potential as an anti-cancer agent. The research also implies that these molecules might be potential lead compounds for developing new prostate cancer drugs.
摘要：
通过4-硝基苄基溴与丙二酸及其衍生物的亲核取代反应，设计并合成了新的4-硝基苄基衍生物。使用质量分析和光谱技术对合成的分子进行表征，并使用各种方法测试其抗氧化性能。比如一氧化氮，DPPH,和过氧化氢自由基清除方法。使用RBC膜稳定和白蛋白变性方法评估分子的抗炎活性。我们使用DU145细胞系评估了化合物的潜在抗前列腺癌活性。MTT法测定细胞活力，表明良好的抗增殖活性。分子3c表现出最高的效力，CTC50为11.83µg/mL。进行分子动力学模拟以研究对接后蛋白质内配体的稳定性和所得蛋白质-配体复合物。分子3c在DAL异种移植模型中的体内分析证实了有希望的结果。寿命的增加，肿瘤体积减少，与标准药物相当的效果是令人鼓舞的特征，表明分子3c可能具有作为抗癌药物的显著潜力。该研究还暗示，这些分子可能是开发新的前列腺癌药物的潜在先导化合物。
