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

Abstract

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.

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

“…Ribofuranose derivatives were synthesized from the starting material 3- O -benzyl-4- C -(hydroxymethyl)-1, 2- O -isopropylidene-α-D-ribofuranose ( 1 ) ( Scheme 1 ). Compound 1 was subjected to benzylation at room temperature which yielded di-benzyl derivative 2 along with an undesired tri-benzyl derivative similar to that reported in our previous study ( Rahman et al, 2020 ). Compound 2 was separated from the undesired product and reacted with acetic anhydride to produce acetylated derivative 3 in high yield.…”

“…1 , structure b ) and phenothiazine analogues showed better antimicrobial activity than the analogues alone ( Kumar et al, 2001 ). α-D-ribofuranose analogues and its nucleoside derivatives have many reported pharmacological properties including analgesic, anti-inflammatory, antimicrobial and cytotoxic effect ( Galmarini et al, 2008 , Petrelli et al, 2017 , Rahman et al, 2020 ). Some triazole based D-ribofuranose ( Ferreira et al, 2010 ) and recently isolated α-D-ribofuranose derivatives (for example structure c in Fig.…”

“…Since D-ribose and its analogues showed several biological activities, we became interested to synthesize and investigate the biological properties of D-ribose derivatives. Recently, we have ( Rahman et al, 2020 ) reported potential analgesic and anti-inflammatory activity of some known a-D-ribofuranose derivatives (structure d, Fig. 1 ).…”