Domiati Souraya, El-Mallah Ahmed, Ghoneim Asser, Bekhit Adnan, El Razik Heba Abd
Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Beirut Arab University, Beirut Campus, Tareek El Jadida, Riad El Solh, P.O. Box 11-5020, Beirut, 11072809, Lebanon.
Department of Pharmacology, Faculty of Pharmacy, Pharos University, Alexandria, Egypt.
Inflammopharmacology. 2016 Aug;24(4):163-72. doi: 10.1007/s10787-016-0270-7. Epub 2016 Jun 24.
Non-steroidal anti-inflammatory drugs are associated with several side effects, such as gastrointestinal mucosal damage, renal toxicity, and cardiovascular side effects. Aiming to find a novel analgesic/anti-inflammatory drug with minimal side effects, the present study was designed to screen and evaluate some newly synthesized pyrazole derivatives.
Anti-inflammatory activity using carrageenan-induced rat paw edema and cotton-pellet-induced granuloma, COX-1/COX-2 selectivity using thin layer chromatography, and analgesic using hot plate and tail flick tests as well as ulcerogenic and renal side effects of the ten compounds were assessed.
The results of the carrageenan-induced rat paw edema showed that the carboxyphenylhydrazone derivative (N9) was more potent than the chlorophenyl counterpart (N8) with a relative activity compared to celecoxib of 1.08 and -0.13, respectively, after 1 h. Even though this is true, N9 caused significant increase in the ulcer index, creatinine, and Blood Urea Nitrogen levels. The cotton granuloma test showed that the carboxyphenylhydrazone derivative (N7) was also more potent than its chlorophenyl counterpart (N6) with a relative activity compared to celecoxib of 1.13 and 0.86, respectively. Moreover, adding an acetyl not only increased the anti-inflammatory activity from a relative activity compared to celecoxib of 0.57-1.17 for the compounds X4 and N5, respectively, in the granuloma test, but also increased the selectivity toward COX-2 from 0.197 to 47.979.
As a conclusion, from the ten compounds analyzed, N5 and N7 showed promising results as anti-inflammatory/analgesic agents with low ulcerogenicity and nephrotoxicity and thus should be further analyzed to determine the ED50 and other side effects.
非甾体抗炎药会引发多种副作用，如胃肠道黏膜损伤、肾毒性和心血管副作用。为了找到一种副作用最小的新型镇痛/抗炎药，本研究旨在筛选和评估一些新合成的吡唑衍生物。
采用角叉菜胶诱导的大鼠足肿胀和棉球诱导的肉芽肿模型评估抗炎活性，用薄层色谱法评估COX - 1/COX - 2选择性，并用热板法和甩尾试验评估镇痛作用，同时评估这10种化合物的致溃疡和肾脏副作用。
角叉菜胶诱导的大鼠足肿胀实验结果显示，羧基苯腙衍生物（N9）比氯苯基类似物（N8）更有效，1小时后与塞来昔布相比的相对活性分别为1.08和 - 0.13。尽管如此，N9导致溃疡指数、肌酐和血尿素氮水平显著升高。棉球肉芽肿试验表明，羧基苯腙衍生物（N7）也比其氯苯基类似物（N6）更有效，与塞来昔布相比的相对活性分别为1.13和0.86。此外，引入一个乙酰基不仅在肉芽肿试验中使化合物X4和N5与塞来昔布相比的抗炎活性分别从0.57提高到1.17，而且使对COX - 2的选择性从0.197提高到47.979。
总之，在所分析的10种化合物中，N5和N7作为具有低致溃疡性和肾毒性的抗炎/镇痛药显示出有前景的结果，因此应进一步分析以确定其半数有效量及其他副作用。
