A new acyl derivative of sulfadimethoxine inhibits phagocyte oxidative burst and ameliorates inflammation in a mice model of zymosan-induced generalised inflammation.
Tariq Ahmad BaigHaroon M HaniffaHina SiddiquiSyeda Farah ShahAlmas JabeenPublished in: Inflammopharmacology (2023)
Chronic inflammation and oxidative stress play a pivotal role in the pathophysiology of most challenging illnesses, including cancer, Alzheimer's, cardiovascular and autoimmune diseases. The present study aimed to investigate the anti-inflammatory potential of a new sulfadimethoxine derivative N-(4-(N-(2,6-dimethoxypyrimidin-4-yl) sulfamoyl) phenyl) dodecanamide (MHH-II-32). The compound was characterised by applying 1 H-, 13 C-NMR, EI-MS and HRFAB-MS spectroscopic techniques. The compound inhibited zymosan-induced oxidative bursts from whole blood phagocytes and isolated polymorphonuclear cells with an IC 50 value of (2.5 ± 0.4 and 3.4 ± 0.3 µg/mL), respectively. Furthermore, the inhibition of nitric oxide with an IC 50 (3.6 ± 2.2 µg/mL) from lipopolysaccharide-induced J774.2 macrophages indicates its in vitro anti-inflammatory efficacy. The compound did not show toxicity towards normal fibroblast cells. The observational findings, gross anatomical analysis of visceral organs and serological tests revealed the non-toxicity of the compound at the highest tested intraperitoneal (IP) dose of 100 mg/kg in acute toxicological studies in Balb/c mice. The compound treatment (100 mg/kg) (SC) significantly (P < 0.001) downregulated the mRNA expression of inflammatory markers TNF-α, IL-1β, IL-2, IL-13, and NF-κB, which were elevated in zymosan-induced generalised inflammation (IP) in Balb/c mice while upregulated the expression of anti-inflammatory cytokine IL-10, which was reduced in zymosan-treated mice. No suppressive effect was observed at the dose of 25 mg/kg. Ibuprofen was taken as a standard drug. The results revealed that the new acyl derivative of sulfadimethoxine has an immunomodulatory effect against generalised inflammatory response with non-toxicity both in vitro and in vivo, and has therapeutic potential for various chronic inflammatory illnesses.
Keyphrases
- oxidative stress
- diabetic rats
- induced apoptosis
- anti inflammatory
- inflammatory response
- lipopolysaccharide induced
- drug induced
- high fat diet induced
- ischemia reperfusion injury
- nitric oxide
- high glucose
- dna damage
- mass spectrometry
- multiple sclerosis
- insulin resistance
- rheumatoid arthritis
- cell cycle arrest
- poor prognosis
- squamous cell carcinoma
- ms ms
- mouse model
- liver failure
- magnetic resonance
- high resolution
- adipose tissue
- hydrogen peroxide
- immune response
- molecular docking
- young adults
- single cell
- heat shock
- electronic health record
- cell proliferation
- case control
- fatty acid
- toll like receptor
- skeletal muscle
- cross sectional
- wild type
- mild cognitive impairment
- adverse drug
- oxide nanoparticles
- climate change
- nitric oxide synthase