Design and synthesis of N-aryl-phthalimides as inhibitors of glucocorticoid-induced TNF receptor-related protein, pro-inflammatory mediators and cytokines in carrageenan-induced lung inflammation

Journal Article

Ahmad, 3. Mashooq A. Bhat, Mohamed A. Al-Omar, Mushtaq A. Ansari, Khairy M. A. Zoheir, Faisal Imamb, Sabry M. Attia, Saleh A. Bakheet, Ahmed Nadeem, Hesham M. Korashy, Andrey Voronkov, Vladimir Berishvili, Sheikh F. . 2015

• المجلة \ الصحيفة: Journal of Medicinal Chemistry
• رقم العدد: 22
• رقم الإصدار السنوي: 58
• الصفحات: 8850-8867

مستخلص المنشور

N-Arylphthalimides (1−10P) derived from thalidomide
by insertion of hydrophobic groups were evaluated for
anti-inflammatory activity, and (4-(1,3-dioxo-1,3-dihydro-2Hisoindol-
2-yl)-N′-[(4-ethoxyphenyl)methylidene]benzohydrazide
6P was identified as a promising anti-inflammatory agent. Further
testing confirmed that compared with the control, 6P treatment
resulted in a considerable decrease in CD4+, NF-κB p65+, TNF-
α+, IL-6+, GITR+, and IL-17+ cell populations and an increase in
the Foxp3+, CD4+Foxp3+, and IκBα+ populations in whole blood
and pleural fluid of a mouse model of lung inflammation.
Moreover, treatment with compound 6P decreased the proteins
associated with inflammation including TNF-α, IL-6, IL-17,
GITR, NF-κB, COX-2, STAT-3, and iNOS and increased the
anti-inflammatory mediators such as IL-10 and IL-4. Further, histopathological examination confirmed the potent antiinflammatory
effects of compound 6P. Thus, the N-arylphthalimide derivative 6P acts as a potent anti-inflammatory agent in the
carrageenan-induced lung inflammation model, suggesting that this compound may be useful for the treatment of inflammation
in a clinical setting