Synthesis, characterization and preliminary pharmacological evaluation of new non-steroidal anti-inflammatory pyrazoline derivatives

Abstract

A series of six pyrazoline ring derivatives as a pharmacophore were incorporated to the naproxen; to increase its size were synthesized and preliminarly evaluated as antiinflammatory agents with expected selectivity toward COX-2 enzyme. In vivo acute antiinflammatory effects of the final compounds (5a-f) were evaluated in rats using egg-white induced edema model of inflammation. The tested compounds and the reference drug (naproxen) produced significant reduction of paw edema with respect to the effect of control group (propylene glycol 50%, v:v). However, compound 5d and 5e show comparable effect to naproxen at all experimental time while compounds 5a, 5b and 5c produced significantly lower inhibitory effect than naproxen at time 120-240 minutes. Furthermore, compound 5f exert significantly higher paw edema reduction than naproxen at 60-240 min. Also the antibacterial activities of the final compounds were evaluated by Well Diffusion Method. All tested compounds exert significant antibacterial activity against tested Gram positive and Gram negative bacteria in comparison to dimethyl sulfoxide as control group. In comparison the antibacterial results among the tested compound 5e may regard the best one and compound 5c the lower one.

TRIAZOLOTHIADIAZOLES DRIVED FROM IBUPROFEN AND THIOCARBOHYDRAZIDE: Synthesis, Characterization, docking studies, and Preliminary Pharmacological assessment

“…The carrageenan model early phase (1-2 hr.) is mostly mediated by serotonin, histamine in addition elevation in the prostaglandins synthesis in the damaged surroundings tissue, while the late phase is sustained by release of prostaglandin beside is mediated by: bradykinin, polymorph nuclear cells, leukotrienes and prostaglandins produced by macrophages tissue [52].…”

“…Subcutaneous injection of carrageenan into the rat paw produces inflammation resulting from plasma extravasations, increased tissue water and plasma protein exudation along with neutrophil extravasations, all due to the metabolism of AA [52].…”

Naphthyl‐Based Chalcone Derivatives: A Multifaceted Player in Medicinal Chemistry

“…A series of pyrazoline pharmacophores 99 a-f (Figure 17) were incorporated into the carboxylate group of naproxen to synthesize prospective non-steroidal anti-inflammatory drugs by Mahdi et al [148] Compounds 99 a-c, 99 d, and 99 e showed less inhibitory effects than naproxen, while compound 99 f significantly decreased paw edema from 60-240 min. The Well Diffusion Method assessed the antibacterial properties of compounds, revealing significant activity against Gram-positive and Gram-negative microorganisms, with compound 99 e being the most effective.…”

“…A series of pyrazoline pharmacophores 99 a – f (Figure 17) were incorporated into the carboxylate group of naproxen to synthesize prospective non‐steroidal anti‐inflammatory drugs by Mahdi et al [148] . Compounds 99 a – c , 99 d , and 99 e showed less inhibitory effects than naproxen, while compound 99 f significantly decreased paw edema from 60–240 min.…”

Design, synthesis, preliminary pharmacological evaluation, molecular docking and ADME studies of some new pyrazoline, isoxazoline and pyrimidine derivatives bearing nabumetone moiety targeting cyclooxygenase enzyme

“…The oxazoline ring presents an interesting structure on which to build a wide variety of compounds having antioxidant, antimicrobial, anti-inflammatory, antimalarial, antitumor, antiviral, antitubercular, antipyretic, and central nerves system stimulant activities. 27 Pyrimidine derivatives are known to be biologically active compounds and substituted pyrimidines have shown wide range of biological activities such as antitubercular, [28][29][30] antibacterial, [31][32][33] antioxidant, 31 anti-inflammatory activity. 34…”