Drug Discovery of New Anti-Inflammatory Compounds by Targeting Cyclooxygenases

Pharmaceuticals

Shady Burayk¹  Mahmoud Kandeel¹  Kentaro Oh-hashi² 

[1] Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-Hofuf 31982, Saudi Arabia;Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan;

关键词: docking;    non-steroidal anti-inflammatory drugs;    drug discovery;    lipoxygenase;    cyclooxygenase;   

DOI  :  10.3390/ph15030282

来源: DOAJ

【 摘 要 】

The goal of achieving anti-inflammatory efficacy with the fewest possible adverse effects through selective COX-2 inhibition is still being investigated in order to develop drugs with safe profiles. This work shows the efficacy and safety profile of two novel benzimidazole piperidine and phenoxy pyridine derivatives in reaching this goal, which would be considered a major achievement in inflammatory therapy. The compounds were evaluated by virtual screening campaign, in vitro cyclooxygenase 1 and 2 (COX-1 and COX-2) inhibition, in vivo carrageenan-induced rat paw edema assay, cytotoxicity against Raw264.7 cells, and histopathological examination of rat paw and stomach. Two new compounds, compound 1 ([(2-{[3-(4-methyl-1H-benzimidazol-2-yl)piperidin-1-yl]carbonyl}phenyl)amino]acetic acid) and compound 2 (ethyl 1-(5-cyano-2-hydroxyphenyl)-4-oxo-5-phenoxy-1,4-dihydropyridine-3-carboxylate) showed high selectivity against COX-2, favourable drug-likeness and ADME descriptors, a lack of cytotoxicity, relived paw edema, and inflammation without noticeable side effects on the stomach. These two compounds are promising new NSAIDs.

【 授权许可】

Unknown