Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
Department of Pharmaceutical Chemistry, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
BMC Pharmacol Toxicol. 2022 Jul 29;23(1):58. doi: 10.1186/s40360-022-00596-0.
The present study aims to investigate the newly synthesized organotin (IV) complex (2E, 2'E) dibutylstannanediyl bis (4-(4-nitrophenyl) amino)-4-oxobut-2-enoate (DTN) for its anti-ulcer potential. Characterization performed by carbon nuclear magnetic resonance spectroscopy proved that all values are in the expected ranges of the new compound. Gastroprotective activity of DTN was evaluated through in-silico, anti-H. pylori, in-vitro, in-vivo, and ex-vivo proteomic analysis. In-silico analysis shows that DTN possess stable binding with protein targets involved in gastric ulcer pathophysiology. DTN exhibited an inhibitory effect against 2,2-diphenyl-1-picrylhydrazyl, H. pylori and hydrogen potassium ATPase (H/K-ATPase). The antiulcer activity was performed using an ethanol-induced gastric ulcer model in rats. Anti-oxidant profile of DTN showed a significant increase in glutathione-S-transferase, glutathione and catalase levels whereas lipid peroxidation levels were reduced. Histopathological findings confirmed that DTN protected the gastric mucosa of rats. Inflammatory markers tumor necrosis factor-alpha, nuclear factor kappa B, cyclooxygenase-2, interleukin 6 and interleukin-1β were reduced and prostaglandin-E restored expression of these cytokines in DTN pretreated animals when analyzed by using immunohistochemistry, enzyme-linked immunosorbent assay and western blot techniques. In real-time polymerase chain reaction technique, the expression of H/K-ATPase was downregulated in DTN pretreated group. DTN did not cause any mortality up to 400 mg/Kg. This study indicates that the newly synthesized compound DTN, possess stable binding against selected targets. DTN exhibits a gastro-protective effect, mediated via anti-H. pylori, H/K-ATPase inhibition, anti-oxidant and anti-inflammatory pathways, exploring its therapeutic potential in gastric ulcer management.
本研究旨在探讨新合成的有机锡(IV)配合物(2E,2'E)二丁基锡二亚基双(4-(4-硝基苯基)氨基)-4-氧代丁-2-烯酸酯(DTN)的抗溃疡潜力。通过碳核磁共振波谱法进行的表征证明,所有值均在新化合物的预期范围内。通过计算机模拟、抗 H. pylori、体外、体内和离体蛋白质组学分析来评估 DTN 的胃保护活性。计算机模拟分析表明,DTN 与参与胃溃疡病理生理学的蛋白质靶标具有稳定的结合。DTN 对 2,2-二苯基-1-苦基肼、H. pylori 和氢钾 ATP 酶(H/K-ATPase)具有抑制作用。在大鼠乙醇诱导的胃溃疡模型中进行抗溃疡活性。DTN 的抗氧化谱显示谷胱甘肽-S-转移酶、谷胱甘肽和过氧化氢酶水平显著增加,而脂质过氧化水平降低。组织病理学发现证实 DTN 保护了大鼠的胃黏膜。通过免疫组织化学、酶联免疫吸附测定和 Western blot 技术分析,炎性标志物肿瘤坏死因子-α、核因子 kappa B、环氧化酶-2、白细胞介素 6 和白细胞介素-1β减少,前列腺素 E 在 DTN 预处理动物中恢复了这些细胞因子的表达。在实时聚合酶链反应技术中,在 DTN 预处理组中 H/K-ATPase 的表达下调。DTN 最高剂量 400mg/Kg 未引起任何死亡。本研究表明,新合成的化合物 DTN 对选定的靶标具有稳定的结合。DTN 通过抗 H. pylori、H/K-ATPase 抑制、抗氧化和抗炎途径发挥胃保护作用,探索其在胃溃疡管理中的治疗潜力。