Anti-Inflammatory and Analgesic Activities of 7-Chloro-4-(Piperazin-1-yl) Quinoline Derivative Mediated by Suppression of InflammatoryMediators Expression in Both RAW 264.7 and Mouse Models

Abstract

Background: 4-Aminoquinoline derivatives possess various potential biological properties.The introduction of additional piperazine heterocyclic pharmacophoric moiety tends to haveprofound impact in increasing the activity. The present work was undertaken to investigate thein-vitro and in-vivo anti-inflammatory activity as well as the peripheral and central analgesicactivities of compound 1-(4-(7-chloroquinoline-4-yl)piperazin-1-yl)-2-(4-phenylpiperazin-1-yl)ethanone (5) in experimental models. Methods: The percentage inhibition of the lipopolysaccharide induced NO release of 7-chloro-4-(piperazin-1-yl)quinoline derivatives 1-9 was determined in RAW 264.7 murine macrophagemodel. Western blot analysis was performed to evaluate the effect of compound 5 on proteinexpression of inducible nitric oxide synthase (iNOS). Gene expression of inflammatory markerswas evaluated using real-time polymerase chain reaction. The peripheral and central analgesicactivities of compound 5 were evaluated in mice using writhing and hot-plate tests, respectively.Anti-inflammatory activity was assessed using carrageenan-induced paw edema assay in miceand serum NO and COX-2 levels were measured. Results: Compound 5 demonstrated the highest NO inhibitory activity that was accompaniedby inhibition of iNOS protein expression and decreased gene expression levels of inflammatorymarkers. It revealed a potential peripheral analgesic effect through inhibition of abdominalwrithing in mice treated with doses of 15 and 30 mg/kg and its effect was comparable to diclofenacsodium. Compound 5 possessed an analgesic activity starting from 15 min post administrationand reached its peak at 45 min which was significantly higher than that of tramadol hydrochloridesuggesting its potential as central analgesic agent. It also showed percentage of inhibition ofedema of 34, 50 and 64% at 1, 2, and 3 h respectively, post carrageenan challenge together with asignificant decrease in serum NO and COX-2 levels. Conclusion: The remarkable anti-inflammatory and analgesic activities of compound 5 couldbe attributed to the advantageous introduction of the heterocyclic 7-chloro-4-(piperazin1-yl)quinoline scaffold incorporated with N-phenylpiperzine functional groups linked together withthe ethanone pharmacophoric chain.

Inflammatory mediators, oxidative stress and genetic disturbance in rheumatoid arthritis rats supported by alfalfa seeds metabolomic constituents via blocking interleukin‐1receptor.

“…Right and left hind paw thickness was measured using Vernier Calliper (SMEC, Shanghai, China) on 7th, 14th, 21st and 28th day of the study period. The percentage of swelling as well as the percent inhibition of edema of the rat paw were calculated using the following equations [22] 1 $$$\vcenter{\openup.5em\halign{$\displaystyle{#}$\cr {\rm Percentage}\ {\rm swelling}=[({\rm Vr}- {\rm Vl})/{\rm V1}]\times 100\hfill\cr}}$$$…”

HPLC and GC–MS–based metabolic profiles and in vivo anticonvulsant, sedative, and antinociceptive potentials of truffles Tirmania nivea and Tirmania pinoyi hydromethanolic extracts in mice

“…Abdominal writhing is a response described as abdominal muscle contraction and pelvic rotations followed by hind limb extension (Aboutabl & Abd El‐Hamid, 2015; Al‐Ashaal et al, 2013). The antinociceptive activity was described as % inhibition of abdominal writhings using the following equation (Aboutabl et al, 2021): Where N c is the mean number of writhes of the control group and N t is the mean number of writhes of the treated group.…”

Chemical Composition and Bioactivities of Egyptian Opuntia ficus–indica Seeds Oils Obtained by Conventional and Ultrasound-assisted Extraction Techniques

“…Throughout the observation period, each mouse's numbers of writhes were counted. Abdominal writhing activity is defined as contraction of the abdominal muscles, rotation of the pelvis, and extension of the hind limbs [34].…”