Synthesis, in vivo and in silico analgesic and anti-inflammatory studies of α-D-ribofuranose derivatives

摘要

Five α-D-ribofuranose analogues ( 2 , 3 , 4, 5 and 6 ) were synthesized in good yields from 3- O -benzyl-4- C -(hydroxymethyl)-1, 2- O -isopropylidene-α-D-ribofuranose ( 1 ). The synthesized compounds were then subjected to analgesic, anti-inflammatory, antimicrobial and antioxidant assays . Compound 3 demonstrated 79.74% ( P ?0.001) writhing inhibition and highest reaction time of 2.55?±?0.13?min ( P ?0.001) after 30?min of oral administration in peripheral and central analgesic assay, respectively, at 50?mg/kg dose. Compound 2 and 6 exhibited significant anti-inflammatory activity at 100?mg/kg dose with paw edema inhibition of 91.15% ( P ?0.001) and 95.13% ( P ?0.001), respectively, in 4th hour. The synthesized analogues did not show notable antioxidant and antibacterial properties. Molecular docking study revealed higher binding affinity of ?8.1?kcal/mol and ?8.9?kcal/mol of compound 3 towards cyclooxygenase-1 and phospholipase A 2, respectively, compared to ?7.7 and ?7.6?kcal/mol respectively for corresponding native ligands. Compound 2 demonstrated binding affinity of ?9.1?kcal/mol towards interleukin-1 receptor-associated kinase-4 compared to ?8.7?kcal/mol of the native ligand. The molecular properties related to drug likeness of compounds were found to be within acceptable range. Synthesized D-ribofuranose analogues demonstrated promising analgesic and anti-inflammatory activities and further development may lead to new potent analgesic and anti-inflammatory agents.