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Evaluation of anti-inflammatory, analgesic activities, and side effects of some pyrazole derivatives

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Abstract

Background and purpose

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.

Method

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.

Results and discussion

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.

Conclusion

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.

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Abbreviations

PG:

Prostaglandin

COX:

Cyclooxygenase

NSAIDs:

Non-steroidal anti-inflammatory drugs

X1, X2, X3, X4, N1, N5, N6, N7, N8, N9:

Products analyzed

BUN:

Blood urea nitrogen

SPSS:

Statistical Package for the Social Science

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Authors and Affiliations

  1. 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

    Souraya Domiati

  2. Department of Pharmacology, Faculty of Pharmacy, Pharos University, Alexandria, Egypt

    Ahmed El-Mallah

  3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Damanhur University, Damanhur, Egypt

    Asser Ghoneim

  4. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt

    Adnan Bekhit & Heba Abd El Razik

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  1. Souraya Domiati
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  2. Ahmed El-Mallah
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  4. Adnan Bekhit
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  5. Heba Abd El Razik
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Correspondence to Souraya Domiati.

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Domiati, S., El-Mallah, A., Ghoneim, A. et al. Evaluation of anti-inflammatory, analgesic activities, and side effects of some pyrazole derivatives. Inflammopharmacol 24, 163–172 (2016). https://doi.org/10.1007/s10787-016-0270-7

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