Novel chalcone/aryl carboximidamide hybrids as potent anti-inflammatory via inhibition of prostaglandin E2 and inducible NO synthase activities: design, synthesis, molecular docking studies and ADMET prediction

Journal of Enzyme Inhibition and Medicinal Chemistry

Amr H. Moustafa¹  Tarek S. Ibrahim²  Ahmad J. Almalki²  Mamdouh F. A. Mohamed³  Shadab Md⁴  Abdulhamid Althagafi⁵  Rasha M. Allam⁶ 

[1] Department of Chemistry, Faculty of Science, Sohag University;Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University;Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University;Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University;Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University;Pharmacology Department, National Research Centre;

关键词: chalcone;    carboximidamide;    inos inhibitors;    anti-inflammatory;    amidoxime;    pge2;   

DOI  :  10.1080/14756366.2021.1929201

来源: DOAJ

【 摘 要 】

Two series of chalcone/aryl carboximidamide hybrids 4a–f and 6a–f were synthesised and evaluated for their inhibitory activity against iNOS and PGE2. The most potent derivatives were further checked for their in vivo anti-inflammatory activity utilising carrageenan-induced rat paw oedema model. Compounds 4c, 4d, 6c and 6d were proved to be the most effective inhibitors of PGE2, LPS-induced NO production, iNOS activity. Moreover, 4c, 4d, 6c and 6d showed significant oedema inhibition ranging from 62.21% to 78.51%, compared to indomethacin (56.27 ± 2.14%) and celecoxib (12.32%). Additionally, 4c, 6a and 6e displayed good COX2 inhibitory activity while 4c, 6a and 6c exhibited the highest 5LOX inhibitory activity. Compounds 4c, 4d, 6c and 6d fit nicely into the pocket of iNOS protein (PDB ID: 1r35) via the important amino acid residues. Prediction of physicochemical parameters exhibited that 4c, 4d, 6c and 6d had acceptable physicochemical parameters and drug-likeness. The results indicated that chalcone/aryl carboximidamides 4c, 4d, 6c and 6d, in particular 4d and 6d, could be used as promising lead candidates as potent anti-inflammatory agents.

【 授权许可】

Unknown