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

Fahad Imtiaz Rahman , Fahad Hussain, Nazmus Saqueeb, S. M. Abdur Rahman

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 (1HNMR), 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.


Keywords


α-D-ribofuranose; Anti-inflammatory; Anti-nociception; Cytotoxicity; Modified derivatives.

Full Text:

PDF

References


Nicolaou KC, Mitchell HJ. Adventures in carbohydrate chemistry: new synthetic technologies, chemical synthesis, molecular design, and chemical biology. Angew Chem Int Ed Engl. 2001;40(9):1576-1624.

DOI: 10.1002/1521-3773.

Mishra S, Upadhaya K, Mishra KB, Shukla AK, Tripathi RP, Tiwari VK. Carbohydrate-based therapeutics: a frontier in drug discovery and development. Studies in Natural Products Chemistry. 2016;49:307-361.

DOI: 10.1016/B978-0-444-63601-0.00010-7.

Bayram M, St Cyr J, Abraham WT. D-ribose aids heart failure patients with preserved ejection fraction and diastolic dysfunction: a pilot study. Ther Adv Cardiovasc Dis. 2015;9(3):56-65.

DOI: 10.1177/1753944715572752.

Thompson J, Neutel J, Homer K, Tempero K, Shah A, Khankari R. Evaluation of D-ribose pharmacokinetics, dose proportionality, food effect, and pharmacodynamics after oral solution administration in healthy male and female subjects. J Clin Pharmacol. 2014;54(5):546-554.

DOI: 10.1002/jcph.241.

Teitelbaum JE, Johnson C, St Cyr J. The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study. J Altern Complement Med. 2006;12(9):857-862.

DOI: 10.1089/acm.2006.12.857.

Omran H, McCarter D, St Cyr J, Lüderitz B. D-ribose aids congestive heart failure patients. Exp Clin Cardiol. 2004;9(2):117-118.

Dhanoa TS, Housner JA. Ribose: more than a simple sugar? Curr Sports Med Rep. 2007;6(4):254-257.

DOI: 10.1007/s11932-007-0041-8.

Pauly DF, Pepine CJ. D-Ribose as a supplement for cardiac energy metabolism. J Cardiovasc Pharmacol Ther. 2000;5(4):249-258.

DOI: 10.1054/JCPT.2000.18011.

Pfundheller HM, Lomholt C. Locked nucleic acids: synthesis and characterization of LNA-T diol. Curr Protoc Nucleic Acid Chem. 2002;8(1):4.12.1-4.12.16.

DOI: 10.1002/0471142700.nc0412s08.

Petrelli R, Scortichini M, Kachler S, Boccella S, Cerchia C, Torquati I, et al. Exploring the role of N6-substituents in potent dual acting 5′-C-ethyltetrazolyladenosine derivatives: synthesis, binding, functional assays, and antinociceptive effects in mice. J Med Chem. 2017;60(10):4327-4341.

DOI: 10.1021/acs.jmedchem.7b00291

Taniho K, Nakashima R, Kandeel M, Kitamura Y, Kitade Y. Synthesis and biological properties of chemically modified siRNAs bearing 1-deoxy-D-ribofuranose in their 3′-overhang region. Bioorganic Med Chem Lett. 2012;22(7):2518-2521.

DOI: 10.1016/j.bmcl.2012.01.132.

Brulíková L, Dubák P, Hajdúch M, Lachnitová L, Kollareddy M, Kolá M, et al. Synthesis of 5-[alkoxy-(4-nitro-phenyl)-methyl]-uridines and study of their cytotoxic activity. Eur J Med Chem. 2010;45(9):3588-3594.

DOI: 10.1016/j.ejmech.2010.05.003.

Atay ÇK, Tilki T, Dede B. Design and synthesis of novel ribofuranose nucleoside analogues as antiproliferative agents: a molecular docking and DFT study. J Mol Liq. 2018;269:315-326.

DOI: 10.1016/j.molliq.2018.08.009.

Hulpia F, Noppen S, Schols D, Andrei G, Snoeck R, Liekens S, et al. Synthesis of a 3′-C-ethynyl-β-d-ribofuranose purine nucleoside library: discovery of C7-deazapurine analogs as potent antiproliferative nucleosides. Eur J Med Chem. 2018;157:248-267.

DOI: 10.1016/j.ejmech.2018.07.062.

Kantham S. Antimicrobial activity of chemoenzymatically prepared ribofuranose derived cationic surfactants. J Pharm Sci & Res. 2011;3(6):1284-1287.

Singh G, Kumar N, Yadav AK, Mishra AK. Syntheses of some new 1,5-benzothiazepine derivatives and their ribofuranosides as antimicrobial agents. Heteroatom Chem. 2002;13(7):620-625.

DOI: 10.1002/hc.10051.

Koshkin AA, Singh SK, Nielsen P, Rajwanshi VK, Kumar R, Meldgaard M, et al. LNA (Locked Nucleic Acids): synthesis of the adenine, cytosine, guanine, 5-methylcytosine, thymine and uracil bicyclonucleoside monomers, oligomerisation, and unprecedented nucleic acid recognition. Tetrahedron. 1998;54(14):3607-3630.

DOI: 10.1016/S0040-4020(98)00094-5.

Rahman SMA, Seki S, Obika S, Yoshikawa H, Miyashita K, Imanishi T. Design, synthesis, and properties of 2′,4′-BNANC: a bridged nucleic acid analogue. J Am Chem Soc. 2008;130(14):4886-4896.

DOI: 10.1021/ja710342q.

Saldanha AA, Siqueira JM, Castro AHF, Matos NA, Klein A, Silva DB, et al. Peripheral and central antinociceptive effects of the butanolic fraction of Byrsonima verbascifolia leaves on nociception-induced models in mice. Inflammopharmacology. 2017;25(1):81-90.

DOI: 10.1007/s10787-016-0300-5.

Muhammad N, Saeed M, Khan H. Antipyretic, analgesic and anti-inflammatory activity of Viola betonicifolia whole plant. BMC Complement Altern Med. 2012;12:59-66.

DOI: 10.1186/1472-6882-12-59.

Zabihi M, Hajhashemi V, Minaiyan M, Talebi A. Evaluation of the central and peripheral effects of doxepin on carrageenan-induced inflammatory paw edema in rat. Res Pharm Sci. 2017;12(4):337-345.

DOI: 10.4103/1735-5362.212052.

Tominaga H, Ishiyama M, Ohseto F, Sasamoto K, Hamamoto T, Suzuki K, et al. A water-soluble tetrazolium salt useful for colorimetric cell viability assay. Anal Commun. 1999;36(2):47-50.

DOI: 10.1039/A809656B.

Srilekha V, Krishna G, Seshasrinivas V, Charya MAS. Antibacterial and anti-inflammatory activities of marine Brevibacterium sp. Res Pharm Sci. 2017;12(4):283-289.

DOI: 10.4103/1735-5362.212045.

Padmapriya R, Ashwini S, Raveendran R. In vitro antioxidant and cytotoxic potential of different parts of Tephrosia purpurea. Res Pharm Sci. 2017;12(1):31-37.

DOI: 10.4103/1735-5362.199044.

Jarvis MF, Yu H, McGaraughty S, Wismer CT, Mikusa J, Zhu C, et al. Analgesic and anti-inflammatory effects of A-286501, a novel orally active adenosine kinase inhibitor. Pain. 2002;96(1-2):107-118.

DOI: 10.1016/S0304-3959(01)00435-3

Boyer SH, Ugarkar BG, Solbach J, Kopcho J, Matelich MC, Ollis K, et al. Adenosine kinase inhibitors. 5. Synthesis, enzyme inhibition, and analgesic activity of diaryl-erythro-furanosyltubercidin analogues. J Med Chem. 2005;48(20):6430-6441.

DOI: 10.1021/jm0503650

El-Gazzar AB, Hafez HN, Nawwar GA. New acyclic nucleosides analogues as potential analgesic, anti-inflammatory, anti-oxidant and anti-microbial derived from pyrimido [4, 5-b] quinolines. Eur J Med Chem. 2009;44(4):1427-1436.

DOI: 10.1016/j.ejmech.2008.09.030

Le Bars D, Gozariu M, Cadden SW. Animal models of nociception. Pharmacol Rev. 2001;53(4):597-652.

Vite MH, Nangude SL, Gorte SM. Anti-inflammatory effect of ethanolic extract of Embelia tsjeriam cottam. Int J Pharm Pharm Sci. 2011;3(4):101-102.

Shewale VD, Deshmukh TA, Patil LS, Patil VR. Anti-Inflammatory activity of Delonix regia (Boj. Ex. Hook). Adv Pharmacol Sci. 2012;2012:1-4.

DOI: 10.1155/2012/789713.

Boison D. Adenosine kinase, epilepsy and stroke: mechanisms and therapies. Trends Pharmacol Sci. 2006;27(12):652-658.

DOI: 10.1016/j.tips.2006.10.008


Refbacks

  • There are currently no refbacks.


Creative Commons LicenseThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.