In Silico Investigation of Some Glucose-Aspirin as COX Inhibitor

Keywords: Anti-inflammatory drug, Cyclooxygenase (COX), Aspirin, Molecular docking,, Sugar esters


Monosaccharide derived glucose-aspirin (GA) can be prepared by conjugation between glucose and aspirin (ASA). The GA is reported to show higher analgesic and anti-inflammatory properties than ASA itself. In this perspective, six GAs which are composed of β-D-glucopyranose, ASA and acetyl groups are considered for the present investigations. The glucose unit in these GAs possesses regular chair conformation with slightly lower dipole moments. Molecular orbitals indicated a higher HOMO-LUMO gap of the molecules. All GAs showed more prone to electrophilic interactions than aspirin. Overall, glucose-aspirin esters are found to have better non-steroidal anti-inflammatory properties than the original aspirin. These GAs are better inhibitors of cyclooxygenase-2 (COX2, 5f19) compared to cyclooxygenase-1 (COX1, 6y3c) indicating that these GAs are potential drug candidates for COX2 related inflammation. Additionally, aspirinyl group at C-6 or C-3 position of the glucopyranose unit is found more suitable for anti-inflammatory activities as compared to C-4 position.


Flower, R. (2003). What are all the things that aspirin does? British Medical Journal, 327, 572–573.

Chen, H., Zhang, S. M., Hernan, M. A., Schwarzschild, M. A., Willett, W. C., Colditz, G. A., Speizer, F. E., & Ascherio, A. (2003). Non-steroidal anti-inflammatory drugs and the risk of Parkinson’s disease. Archives of Neurology, 60, 1059–1064.

Entminan, M., Sudeep, G., & Samii, A. (2003). Effect on non-steroidal anti-inflammatory drugs on risk of Alzheimer’s disease: systematic review and meta-analysis of observational studies. British Medical Journal, 327, 128–130.

Ittaman, S. V., VanWormer, J. J., & Rezkalla, S. H. (2014). The role of aspirin in the prevention of cardiovascular disease. Clinical Medicine & Research, 12(3-4), 147–54.

Bartolucci, A. A., Tendera, M., Howard, G. (2011). Meta-analysis of multiple primary prevention trials of cardiovascular events using aspirin. American Journal of Cardiology, 107, 1796–1801.

Soni, A. (2013). Aspirin use among the adult U.S. non-institutionalized population, with and without indicators of heart disease, 2005. Statistical Brief #129. Agency for Healthcare Research and Quality, Medical Expenditure Panel Survey. Link:

Vane, J. R., & Botting, R. M. (2003). The mechanism of action of aspirin. Thrombosis Research, 110, 255-8.

Mekaj, Y., Daci, F., & Mekaj, A. (2015). New insights into the mechanisms of action of aspirin and its use in the prevention and treatment of arterial and venous thromboembolism. Therapeutics and Clinical Risk Management, 11, 1449-1456.

Miner, J., & Hoffhines, A. (2007). The discovery of aspirin’s antithrombotic effects. Texas Heart Institute Journal, 34(2), 179–186.

Krupski, W. C., Weiss, D. G., Rapp, J. H., Corson, J. D., Hobson, R. W. (1992). Adverse effects of aspirin in the treatment of asymptomatic carotid artery stenosis. Journal of Vascular Surgery, 16(4), 588-600.

Karsh, J. (1990). Adverse reactions and interactions with aspirin. Considerations in the treatment of the elderly patient. Drug Safety, 5(5), 317-27. 199005050-00002

Weinberger, J. (2005). Adverse effects and drug interactions of antithrombotic agents used in prevention of ischaemic stroke. Drugs, 65(4), 461-71.

Jacob, J. N., & Tazawa, M. J. (2012). Glucose–aspirin: Synthesis and in vitro anti-cancer activity studies. Bioorganic & Medicinal Chemistry Letters, 22, 3168–3171.

Jacob, J. N., Badyal, D. K. & Bala, S. (2013). Evaluation of the in vivo anti-inflammatory and analgesic activity of a highly water-soluble aspirin conjugate. Basic & Clinical Pharmacology & Toxicology, 112, 171–174.

Dhavale, D. D., Matin, M. M., Sharma, T., & Sabharwal, S. G. (2003). N-Hydroxyethyl-piperidine and –pyrrolidine homoazasugars: preparation and evaluation of glycosidase inhibitory activity. Bioorganic & Medicinal Chemistry, 11(15), 3295–3305.

Dhavale, D. D., & Matin, M. M. (2004). Selective sulfonylation of 4-C-hyroxymethyl-β-L-threo-pento-1,4-furanose: Synthesis of bicyclic diazasugars. Tetrahedron, 60(19), 4275–4281.

Muhammad, D., Matin, M. M., Miah, S. M. R., Devi, P. (2021). Synthesis, antimicrobial, and DFT studies of some benzyl 4-O-acyl-α-L-rhamnopyranosides. Orbital: The Electronic Journal of Chemistry, 13(3), 250–258.

Matin, M. M., Bhuiyan, M. M. H., Afrin, A., & Debnath, D. C. (2013). Comparative antimicrobial activities of some monosaccharide and disaccharide acetates. Journal of Scientific Research, 5(3), 515–525.

Kabir, A. K. M. S., Matin, M. M., Hossain, A., & Sattar, M. A. (2003). Synthesis and antimicrobial activities of some rhamnopyranoside derivatives. Journal of the Bangladesh Chemical Society, 16(2), 85–93. ISSN: 1022-016X

Matin, M. M. (2014). Synthesis and antimicrobial study of some methyl 4-O-palmitoyl-α-L-rhamnopyranoside derivatives. Orbital: The Electronic Journal of Chemistry, 6(1), 20–28.

Matin, M. M., Bhuiyan, M. M. H., Debnath, D. C., & Manchur, M. A. (2013). Synthesis and comparative antimicrobial studies of some acylated D-glucofuranose and D-glucopyranose derivatives. International Journal of Biosciences, 3(8), 279–287.

Kabir, A. K. M. S., & Matin, M. M. (1994). Regioselective acylation of a derivative of L-rhamonse using the dibutyltin oxide method. Journal of the Bangladesh Chemical Society, 7(1), 73–79. ISSN: 1022-016X

Ali, M., Karim, M. H., & Matin, M. M. (2021). Efficient synthetic technique, PASS predication, and ADMET studies of acylated n-octyl glucopyranosides. Journal of Applied Science & Process Engineering, 8(1), 648–659.

Kabir, A. K. M. S., Matin, M. M., Mridha, M. A. U., & Shahed, S. M. (1998). Antifungal activities of some methyl 6-O-trityl-α-D-mannopyranosides. The Chittagong University Journal of Science, 22(1), 41–46. ISSN: 1561-1167

Kabir, A. K. M. S., Matin, M. M., Sanaullah, A. F. M., Sattar, M. A., & Rahman, M. S. (2001). Antimicrobial activities of some lyxoside derivatives. Bangladesh Journal of Microbiology, 18(1), 89–95. ISSN: 1011-9981

Kabir, A. K. M. S., Matin, M. M., Bhuiyan, M. M. R., Rahim, M. A., Rahman, M. S. (2005). Biological evaluation of some monosaccharide derivatives. International Journal of Agriculture and Biology, 7(2), 218–221. ISSN: 1560-8530

Matin, M. M., & Iqbal, M. Z. (2021). Methyl 4-O-(2-chlorobenzoyl)-α-L-rhamnopyranosides: Synthesis, characterization, and thermodynamic studies. Orbital: The Electronic Journal of Chemistry, 13(1), 19–27.

Matin, M. M., Bhuiyan, M. M. H., Azad, A. K. M. S., Akther, N. (2017). Design and synthesis of benzyl 4-O-lauroyl-α-L-rhamnopyranoside derivatives as antimicrobial agents. Current Chemistry Letters, Vol.6, No.1, 31–40.

Matin, M. M., & Ibrahim, M. (2010). Synthesis of some methyl 4-O-octanoyl-α-L-rhamnopyranoside derivatives. Journal of Applied Sciences Research, 6(10), 1527–1532. ISSN: 1816-157X

Kim, H. J., Kang, S. H., Choi, S. S., & Kim, E. S. (2017). Redesign of antifungal polyene glycosylation: engineered biosynthesis of disaccharide-modified NPP. Applied Microbiology & Biotechnology, 101, 5131–5137.

Matin, M. M., Bhuiyan, M. M. H., Azad, A. K. M. S., & Rashid, M. H. O. (2015). Synthesis of 6-O-stearoyl-1,2-O-isopropylidene-α-D-gluco-furanose derivatives for antimicrobial evaluation. Journal of Physical Science, 26,(1), 1–12. ISSN: 1675-3402

Zago, E., Joly, N., Chaveriat, L., Vincent Lequart, V., & Martin, P., (2021). Enzymatic synthesis of amphiphilic carbohydrate esters: Influence of physicochemical and biochemical parameters, Biotechnology Reports, 30, e00631,

Matin, M. M., Bhuiyan, M. H., Hossain, M. M., & Roshid, M. H. O. (2015). Comparative antibacterial activities of some monosaccharide and disaccharide benzoates. Orbital: The Electronic Journal of Chemistry, 7(2), 160–167.

Matin, M. M. (2006). Synthesis of some silyl protected 1,4-galactonolactone derivatives. Journal of Applied Sciences Research, 2(10), 753–756. ISSN: 1816-157X

Chowdhury, A. Z. M. S., & Matin, M. M. (1997). Synthesis of imidazo[1,2-c]pyrido[4¢,3¢:4,5]thieno[3,2-e]-pyrimidine. Chittagong University Studies, Part II: Science, 21(2), 47–52. ISSN: 0253-5459

Khairulzaim, A. A. B. M., Rahman, M. R., Roslan, L., Bakri, M. K. B., Khan, A., Matin, M. M. (2021). Analysis of char prepared by pyrolysis of dabai (Canarium odontophyllum) nutshells as a potential precursor of biocarbon used for wastewater treatment. BioResources, 16(3), 5036–5046.

Santos, C. B. R., Lobato, C. C., Braga, F. S., Morais, S. S. S., Santos, C. F., Fernandes, C. P., Brasil, D. S. B., Hage-Melim, L. I. S., Macedo, W. J. C., & Carvalho, J. C. T. (2014). Application of Hartree-Fock method for modeling of bioactive molecules using SAR and QSPR, Computational Molecular Bioscience, 4, 1–24.

Matin, M. M., Uzzaman, M., Chowdhury, S. A., & Bhuiyan, M. M. H. (2020). In vitro antimicrobial, physicochemical, pharmacokinetics, and molecular docking studies of benzoyl uridine esters against SARS-CoV-2 main protease. Journal of Biomolecular Structure and Dynamics, 1-13.

Matin, M. M., Hasan, M. S., Uzzaman, M., Bhuiyan, M. M. H., Kibria, S. M., Hossain, M. E., & Roshid, M. H. O. (2020). Synthesis, spectroscopic characterization, molecular docking, and ADMET studies of mannopyranoside esters as antimicrobial agents. Journal of Molecular Structure, 1222, 128821.

Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., et al. (2013). Gaussian 09W, Revision D.01. Gaussian, Inc., Wallingford CT.

Matin, M. M., Chakraborty, P., Alam M. S., Islam, M. M., & Hanee, U. (2020) Novel mannopyranoside esters as sterol 14α-demethylase inhibitors: Synthesis, PASS predication, molecular docking, and pharmacokinetic studies. Carbohydrate Research, 496, 108130.

Pehkonen, S. O., & Yuan, S. (2018). Chapter 1 - Introduction and Background. Interface Science and Technology, 23, 1-11.

Matin, M. M., Bhuiyan, M. M. H., Kabir, E., Sanaullah, A. F. M., Rahman, M. A., Hossain, M. E., & Uzzaman, M. (2019). Synthesis, characterization, ADMET, PASS predication, and antimicrobial study of 6-O-lauroyl mannopyranosides. Journal of Molecular Structure, 1195, 189–197.

Filimonov, D.,A., Lagunin, A. A., Gloriozova, T. A., Rudik, A. V., Druzhilovskii, D. S., Pogodin, P. V., Poroikov, V. V. (2014). Prediction of the biological activity spectra of organic compounds using the PASS online web resource. Chemistry of Heterocyclic Compounds, 50(3), 444–457.

Matin, M. M., Bhattacharjee, S. C., Chakraborty, P., & Alam M. S. (2019). Synthesis, PASS predication, in vitro antimicrobial evaluation and pharmacokinetic study of novel n-octyl glucopyranoside esters. Carbohydrate Research, 485, 107812.

Devi, P., Matin, M. M., Bhuiyan, M. M. H., & Hossain, M. E. (2021). Synthesis, and spectral characterization of 6-O-octanoyl-1,2-O-isopropylidene-α-D-glucofuranose derivatives. Journal of the Turkish Chemical Society Section A: Chemistry, 8(4), 1003-1024.

Bakri, M. K. B., Rahman, M. R., & Matin, M. M. (2021). Cellulose reinforcement in thermoset composites. In: Fundamentals and Recent Advances in Nanocomposites Based on Polymers and Nanocellulose, MR Rahman (Ed), 1st Ed, Elsevier Science, 127-142.

Taib, N-. A. B., Rahman, M. R., Bakri, M. K. B., & Matin, M. M. (2021). Advanced techniques for characterizing cellulose. In: Fundamentals and Recent Advances in Nanocomposites Based on Polymers and Nanocellulose, MR Rahman (Ed), 1st Ed, Elsevier Science, 2021, 53-84.

Islam, N., Islam, M. D., Rahman, M. R., & Matin, M. M. (2021). Octyl 6-O-hexanoyl-β-D-glucopyranosides: Synthesis, PASS, antibacterial, in silico ADMET, and DFT studies. Current Chemistry Letters, 10(4), 413-426.

Rahim, A., Bhuiyan, M. M. H., & Matin, M. M. (2020). Microwave assisted efficient synthesis of some flavones for antimicrobial and ADMET studies. Journal of Scientific Research, 12(4), 673-685.

Fraga, C. A. M. (2001). Razões da Atividade Biológica: Interações Micro- e Biomacromoléculas. Química Nova na Escola, São Paulo-SP, 33–42.

How to Cite
Chowdhury, M. A. I., Anisa, T. R., Bhattacharjee, S. C., & Das , S. (2022). In Silico Investigation of Some Glucose-Aspirin as COX Inhibitor. Journal of Applied Science & Process Engineering, 9(1), 1031-1041.