Synthesis and evaluation of pharmacological activities of some 3-O-benzyl-4-C-(hydroxymethyl)-1,2-O-isopropylidene-α-D-ribofuranose derivatives as potential anti-inflammatory agents and analgesics.

BACKGROUND AND PURPOSE: α-D-ribofuranose analogues are reported to have multifarious biological properties such as analgesic, anti-inflammatory, and antiviral activities. The present study aims to synthesize some α-D- ribofuranose derivatives and investigate their biological properties. EXPERIMENTAL APPROACH: Four derivatives (2a, 2b, 3, and 4) were synthesized from the starting material 3-O- benzyl-4-C-(hydroxymethyl)-1,2-O-isopropylidene-α-D-ribofuranose via subsequent benzylation, tosylation, and acetylation reactions in good yields. The compounds were confirmed by spectroscopic methods such as Fourier-transform infrared (FTIR) and proton nuclear magnetic resonance ((1)HNMR), and then evaluated for various pharmacological activities using standard in vitro and in vivo procedures. FINDINGS / RESULTS: Compound 2a (50 mg/kg) exhibited both central and peripheral analgesic activity in the tail immersion test (2.52 ± 0.14 min tail flicking reaction time after 30 min from administration, P < 0.001) and the acetic acid-induced writhing test (65.33 ± 2.06% reduction in abdominal writhing, P < 0.001) respectively. In the anti-inflammatory assay, percent paw edema inhibition of carrageenan-induced rats for compounds 2a and 4 (100 mg/kg) after 4 h of administration were 82.6% (P < 0.001) and 87.6% (P < 0.001), respectively. The compounds were also tested for antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, antimicrobial property in disk diffusion assay, and cytotoxicity in HeLa cell line; however, no significant results were observed in any of those tests. CONCLUSION AND IMPLICATIONS: Our study indicated that some of the synthesized compounds exhibited promising analgesic and anti-inflammatory effects and may serve as potential lead compounds.