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

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.

     

Knowledge of and readiness for medication therapy management among community pharmacists in Lebanon

International Journal of Clinical Pharmacy - Background To follow international standards, the Lebanese Order of Pharmacists would like to start to implement the medication therapy management in...     

Elucidation of the molecular mechanism underlying the anti-inflammatory activity of an effective and safe bipyrazole-based compound

Introduction

Since the synthesis of acetylsalicylic acid by Hoffmann in 1897, new classes of NSAIDs have been introduced; however, their side effects have limited their clinical applications. Consequently, our team has recently synthesized a novel bipyrazole compound that showed a satisfactory efficacy and safety profile. The aim of the current study was to elucidate the molecular mechanism of this bipyrazole compound.

Method

The anti-inflammatory efficacy of the compound was assessed using formalin-induced paw edema test. Computer-assisted simulation docking experiments were carried out. Cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), tumor necrosis factor-alpha (TNFα), interleukin-1 (IL1) and interleukin-10 (IL10) gene expression were quantified with real-time polymerase chain reaction (RT-PCR) using SYBR Green technology. The samples were taken from the plantar paw of mice after formalin local injection.

Results

The efficacy of the bipyrazole compound was similar to that of indomethacin, diclofenac, and celecoxib, as proven by the formalin-induced paw edema. Docking study indicated a superior binding score for the studied compound relative to celecoxib, indomethacin, and diclofenac. RT-PCR assessment revealed a significant decrease in iNOS, COX-2, and TNFα gene expression in the bipyrazole-treated group. Moreover, a reduction in IL1 and nNOS gene expression levels and an increase in IL10 level were detected despite being insignificant compared to the control group.

Conclusion

These findings revealed the superiority of the newly synthesized bipyrazole compound not only on the binding site, but also by inhibiting most of the inflammatory mediators including TNF-α.

     

Study of the effect of using mini-transitional implants as temporary abutments in implant overdenture cases

In an attempt to improve patient satisfaction during the healing period after placement of implants, mini-transitional implants (MTIs) have been advocated to allow immediate use of temporary dentures and to prevent transmucosal loads over the definitive implants. Twelve edentulous patients received two screw implants each in the predetermined mandibular canine region. At the time of surgery, six patients had two MTIs placed medially to the permanent ones. The flap was repositioned allowing transmucosal penetration of MTIs. Patients left the operating room wearing their relined lower dentures. The results indicated that MTIs integrated sufficiently in bone, giving successful immediate support for the transitional prosthesis and allowing proper mucosal healing. Two of these transitional implants showed mobility three months after phase I surgery. After loading the final implants, patients who had MTI-supported dentures showed bone loss that was not significantly different from the control group.