Molecularly diverse lonazolac-inspired pyrazole-cyanopyridin-2-one conjugates: design, synthesis, in vitro, in vivo and in silico studies as multi-target anti-inflammatory agents. (PubMed, Mol Divers) - May 10, 2026 - "In the LPS-induced RAW 264.7 cell line, nitric oxide (NO) inhibitory activity revealed that 4b, 4e, and 5c were the most powerful NO inhibitors, with % inhibition of 64.97, 71.45 and 73.61, respectively, compared with indomethacin (60.97). Hybrids 4f (IC50 = 2.64 µM) and 5e (IC50 = 0.34 µM) were the most potent COX-2 inhibitors with selectivity indexes of 8.1 and 12.6, respectively, compared with Celecoxib (IC50 = 1.33 µM, SI = 4.8), while 4e and 5c were the most potent 5-LOX inhibitors, with IC50 values of 2.75 and 0.71 µM, respectively, compared to the zileuton (IC50 = 0.45 µM)...It could be preliminarily suggested that conjugates 4e and 5c could be considered as NO/5-LOX inhibitor, while conjugate 4f is a selective COX-2/5-LOX inhibitor, and 5e is a selective COX-2 inhibitor. These results indicate that 4e, 5c, and 4f are promising multitarget anti-inflammatory candidates..."
Journal • Preclinical • Inflammation • IL1B • TNFA
|
|
Ahdab N Khayyat; Azizah M Malebari; Deiaa E Elsayed Abouzed; Gamal El-Din A Abuo-Rahma; Majed Alharbi; Mamdouh F A Mohamed; Marwa A Aziz; Mohamed F Radwan; Rasha M Allam; Tarek S Ibrahim
|