研究 N-异丙烯酰咪唑锌络合物衍生物的抗炎、镇痛、致溃疡和抗溃疡活性

Q3 Pharmacology, Toxicology and Pharmaceutics
P. Galenko-Yaroshevsky, O. V. Shelemekh, V. Popkov, Andrey V. Zadorozhniy, Irina B. Nektarevskaya, Natalia D. Bunyatyan, Roman A. Murashko, S. Lebedeva, A. Zelenskaya, Aleksandr V. Uvarov, O. N. Gulevskaya, Lusine O. Alukhanyan, Tereza R. Glechyan, Alina V. Sergeeva, Alina V. Kornetskaya, Nikolay E. Korovaykin
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引用次数: 0

摘要

导言:尽管非甾体抗炎药(NSAIDs)具有明显的治疗效果,但它们也会产生严重的副作用。其中最严重的副作用是致溃疡,可导致生活质量下降甚至死亡。这就需要寻找和创造具有强效抗炎特性,但不会对消化系统产生不良影响的新型化合物。本研究旨在探讨 N-异丙烯基咪唑锌络合物衍生物的抗炎、镇痛、致溃疡和抗溃疡活性:大鼠和小鼠实验用于确定 N-异丙烯酰亚胺唑锌络合物衍生物(实验室名称 Pilim-1)的中位致死剂量 LD50。实验中使用了急性渗出性炎症和慢性增殖性炎症模型。在第一种情况下,向大鼠的后爪注射角叉菜胶和完全弗氏佐剂,诱发炎症。第二种情况是在大鼠皮下植入无菌棉球("棉球诱发肉芽肿")诱发炎症。大鼠的急性和强直性疼痛、内脏疼痛和躯体深部疼痛分别通过福尔马林试验和醋酸诱导的小鼠蠕动试验进行模拟。在大鼠实验中研究了 Pilim-1 的致溃疡作用和抗溃疡作用。结果和讨论:Pilim-1 具有明显的抗炎和镇痛作用,毒性低于双氯芬酸和吲哚美辛,其活性与双氯芬酸相当,优于吲哚美辛。它的治疗指数高于吲哚美辛和双氯芬酸,相反,它基本上没有致溃疡作用,而且比法莫替丁具有更强的抗溃疡活性。由此看来,Pilim-1 的抗炎、镇痛和胃保护特性主要是由于其抗氧化和抗缺氧特性、对环氧化酶和 5-脂氧合酶的抑制作用,以及其结构中含有咪唑和锌,而这两种物质都具有广泛的生物活性:结论:与双氯芬酸和吲哚美辛相比,Pilim-1 的溃疡活性相对较低(几乎没有),具有较强的抗炎、镇痛和抗溃疡作用,治疗指数较高,急性毒性较小,因此可推荐用于进一步的临床前研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Study of the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activity of N-isopropenylimidazole zinc complex derivative
Introduction: Although nonsteroidal anti-inflammatory drugs (NSAIDs) have a clear therapeutic benefit, they can also have serious side effects. The most serious of these is the ulcerogenic effect, which can result in a decline in the quality of life or even death. This calls for the search for and creation of novel compounds with potent anti-inflammatory properties that do not have adverse effects on the digestive system. The aim of the study was to investigate the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activities of N-isopropenylimidazole zinc complex derivative. Materials and Methods: Experiments in rats and mice were used to determine the median lethal dose LD50 for N-isopropenylimidazole zinc complex derivative (laboratory name Pilim-1). Experimental models of acute exudative inflammation and chronic proliferative inflammation were used. In the first case, the inflammation was induced by sub-plantar injection of carrageenan and a complete Freund’s adjuvant into the hind paw of rats. In the second case, the inflammation was induced by the implantation of a sterile cotton pellet (“cotton pellet–induced granuloma”) under the skin of rats. Acute and tonic pain, visceral, and somatic deep pain were simulated using the formalin test in rats and the acetic acid-induced writhing test in mice, respectively. The ulcerogenic and anti-ulcerogenic effects of Pilim-1 were studied in rat experiments. Pilim-1 and the reference drugs diclofenac, indomethacin and famotidine were administered intragastrically. Results and Discussion: Pilim-1 showed marked anti-inflammatory and analgesic effects, demonstrated less toxicity than diclofenac and indomethacin, while its activity is comparable to diclofenac and superior to indomethacin. Its therapeutic index is higher than that of indomethacin and diclofenac and, in contrast, it essentially has no ulcerogenic effect and exhibits stronger anti-ulcerogenic activity than famotidine. It appears that the anti-inflammatory, analgesic, and gastroprotective properties of Pilim-1 are largely due to its antioxidant and antihypoxic properties, its inhibitory effects on cyclooxygenase and 5-lipoxygenase, and the presence of imidazole and zinc in its structure, both of which have a wide range of biological activity. Conclusion: Pilim-1 can be recommended for further preclinical studies due to its relatively low (practically absent) ulcerative activity, strong anti-inflammatory, analgesic, and anti-ulcerative effects, greater therapeutic index, and less acute toxicity in comparison with diclofenac and indomethacin.
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来源期刊
Research Results in Pharmacology
Research Results in Pharmacology Medicine-Pharmacology (medical)
CiteScore
1.50
自引率
0.00%
发文量
32
审稿时长
12 weeks
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