Skip to main content
SpringerLink
Log in

D-Glucosamine is a Potential Urease Inhibitor from Middle Eastern Medicinal Plants for Combatting Helicobacter Pylori Infections; a Molecular Docking and Simulation Approach

  • Original Article
  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

Helicobacter pylori stands as a significant risk factor for both peptic and stomach ulcers. Their resistance to the highly acidic host environment primarily stems from their capability to produce urease, an enzyme that rapidly converts urea into NH3 and CO2. These byproducts are crucial for the bacterium’s survival under such harsh conditions. Given the pivotal role of medicinal plants in treating various ailments with minimal side effects, there is an urgent need for a natural drug that can effectively eliminate H. pylori by inhibiting urease. Hence, the current study aims to identify the most potent urease inhibitor among the natural compounds found in Middle Eastern medicinal plants, taking into consideration factors such as optimal affinity, drug-like properties, pharmacokinetic characteristics, and thermodynamic attributes. In total, 5599 ligand conformers from 151 medicinal plants were subjected to docking against the urease’s active site. The top-ranking natural compounds, as determined by their high docking scores, were selected for further analysis. Among these compounds, D-glucosamine (PubChem code 439,213) exhibited the most interactions with the crucial amino acid residues in the urease’s active site. Furthermore, D-glucosamine demonstrated superior absorption, distribution, metabolism, excretion, and toxicity properties compared to other top-ranked candidates. Molecular dynamics simulations conducted over 100 nanoseconds revealed stable root mean square deviations and fluctuations of the protein upon complexation with D-glucosamine. Additionally, the radius of gyration and solvent-accessible surface area values for the D-glucosamine-urease complex were notably lower than those observed in other typical urease-inhibitor complexes. In conclusion, this study provides valuable insights into the potential development of D-glucosamine as a novel urease inhibitor. This promising compound holds the potential to serve as an effective drug for combating H. pylori infections in the near future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data Availability

The docking structures and Excel spreadsheet are available upon request from the corresponding author.

References

  • Akada JK, Shirai M, Takeuchi H et al (2000) Identification of the urease operon in Helicobacter pylori and its control by mRNA decay in response to pH. Mol Microbiol 36:1071–1084

    Article  CAS  PubMed  Google Scholar 

  • Al-Shuhaib MBS, Hashim HO, Al-Shuhaib JMB (2021a) Epicatechin is a promising novel inhibitor of SARS-CoV-2 entry by disrupting interactions between angiotensin-converting enzyme type 2 and the viral receptor binding domain: a computational/simulation study. Comput Biol Med 141:105155. https://doi.org/10.1016/j.compbiomed.2021.105155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Al-Shuhaib MBS, Hashim HO, Al-Shuhaib JMB (2021b) In silico Discovery of a new potent inhibitor for sterol 14-alpha demethylase as a promising antifungal drug against aspergillus fumigatus infection. Biointerface Res Appl Chem 12:5785–5796

    Article  Google Scholar 

  • Al-Shuhaib MBS, Hashim HO, Al-Shuhaib JMB, Obayes DH (2022) Artecanin of Laurus nobilis is a novel inhibitor of SARS-CoV-2 main protease with highly desirable druglikeness. J Biomol Struct Dyn 41:2355–2367

    Article  PubMed  Google Scholar 

  • Al-Shuhaib MBS, Alam S, Khan SA et al (2023a) Masoprocol: a promising candidate for targeting insulin resistance by inhibiting resistin with optimal druglikeness Potentials: an in silico approach. J Biomol Struct Dyn. https://doi.org/10.1080/07391102.2023.2254842

    Article  PubMed  Google Scholar 

  • Al-Shuhaib MBS, Alam S, Khan SA et al (2023b) Hemagglutinin 3 and 8 can be the most efficient influenza subtypes for human host invasion; a comparative in silico approach. J Biomol Struct Dyn. https://doi.org/10.1080/07391102.2023.2280674

    Article  PubMed  Google Scholar 

  • Asnaashari S, Dastmalchi S, Javadzadeh Y (2018) Gastroprotective effects of herbal medicines (roots). Int J Food Prop 21:902–920

    Article  Google Scholar 

  • Awaad AS, El-Meligy RM, Soliman GA (2013) Natural products in treatment of ulcerative colitis and peptic ulcer. J Saudi Chem Soc 17:101–124

    Article  CAS  Google Scholar 

  • Ayala G, Escobedo-Hinojosa WI, de la Cruz-Herrera CF, Romero I (2014) Exploring alternative treatments for Helicobacter pylori infection. World J Gastroenterol WJG 20:1450

    Article  CAS  PubMed  Google Scholar 

  • Bansal Y, Silakari O (2012) The therapeutic journey of benzimidazoles: a review. Bioorg Med Chem 20:6208–6236

    Article  CAS  PubMed  Google Scholar 

  • Bharatam PV (2021) Computer-aided drug design. Drug Discov Dev from Targets Mol to Med 1:137–210

    Google Scholar 

  • Brenk R, Schipani A, James D et al (2008) Lessons learnt from assembling screening libraries for drug discovery for neglected diseases. ChemMedChem Chem Enabling Drug Discov 3:435–444

    CAS  Google Scholar 

  • Chandrasekaran B, Abed SN, Al-Attraqchi O et al (2018) Computer-aided prediction of pharmacokinetic (ADMET) properties. Dosage form design parameters. Elsevier, New York, pp 731–755

    Chapter  Google Scholar 

  • Colzato LS, Ruiz MJ, van den Wildenberg WPM, Hommel B (2011) Khat use is associated with impaired working memory and cognitive flexibility. PLoS ONE 6:e20602

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Cunha ES, Chen X, Sanz-Gaitero M et al (2021) Cryo-EM structure of Helicobacter pylori urease with an inhibitor in the active site at 2.0 Å resolution. Nat Commun 12:1–8

    Article  Google Scholar 

  • El-Dien RTM, Maher SA, Abdelmohsen UR et al (2020) Antiulcer secondary metabolites from Elaeocarpus Grandis, family Elaeocarpaceae, supported by in silico studies. RSC Adv 10:34788–34799

    Article  ADS  Google Scholar 

  • Essmann U, Perera L, Berkowitz ML et al (1995) A smooth particle mesh Ewald method. J Chem Phys 103:8577–8593

    Article  ADS  CAS  Google Scholar 

  • Follmer C (2010) Ureases as a target for the treatment of gastric and urinary infections. J Clin Pathol 63:424–430

    Article  CAS  PubMed  Google Scholar 

  • Friesner RA, Banks JL, Murphy RB et al (2004) Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem 47:1739–1749

    Article  CAS  PubMed  Google Scholar 

  • Galvin R, Cousins G, Boland F et al (2013) Prescribing patterns of glucosamine in an older population: a national cohort study. BMC Complement Altern Med 13:1–6

    Article  Google Scholar 

  • Ge R-G, Wang D-X, Hao M-C, Sun X-S (2013) Nickel trafficking system responsible for urease maturation in Helicobacter pylori. World J Gastroenterol WJG 19:8211

    Article  CAS  PubMed  Google Scholar 

  • Ha N-C, Oh S-T, Sung JY et al (2001) Supramolecular assembly and acid resistance of Helicobacter pylori urease. Nat Struct Biol 8:505–509

    Article  CAS  PubMed  Google Scholar 

  • Harrach MF, Drossel B (2014) Structure and dynamics of TIP3P, TIP4P, and TIP5P water near smooth and atomistic walls of different hydroaffinity. J Chem Phys 140:174501

    Article  ADS  PubMed  Google Scholar 

  • Harvey MJ, De Fabritiis G (2009) An implementation of the smooth particle mesh Ewald method on GPU hardware. J Chem Theory Comput 5:2371–2377

    Article  CAS  PubMed  Google Scholar 

  • Hassan STS, Šudomová M (2017) The development of urease inhibitors: what opportunities exist for better treatment of Helicobacter pylori infection in children? Children 4:2

    Article  PubMed  PubMed Central  Google Scholar 

  • Khan S, Ullah H, Rahim F et al (2023) Synthesis, biological evaluation and molecular docking study of pyrimidine based thiazolidinone derivatives as potential anti-urease and anti-cancer agents. J Saudi Chem Soc 27:101688

    Article  CAS  Google Scholar 

  • Krieger E, Vriend G (2015) New ways to boost molecular dynamics simulations. J Comput Chem 36:996–1007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krieger E, Nielsen JE, Spronk CAEM, Vriend G (2006) Fast empirical pKa prediction by Ewald summation. J Mol Graph Model 25:481–486

    Article  CAS  PubMed  Google Scholar 

  • Kuna L, Jakab J, Smolic R et al (2019) Peptic ulcer disease: a brief review of conventional therapy and herbal treatment options. J Clin Med 8:179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Land H, Humble MS (2018) YASARA: a tool to obtain structural guidance in biocatalytic investigations. Protein Engineering. Springer, Berlin, pp 43–67

    Chapter  Google Scholar 

  • Liang B, Yuan Y, Peng X-J et al (2022) Current and future perspectives for Helicobacter pylori treatment and management: from antibiotics to probiotics. Front Cell Infect Microbiol 12:1740

    Article  Google Scholar 

  • Lipinski CA (2004) Lead-and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol 1:337–341

    Article  CAS  PubMed  Google Scholar 

  • Loughlin MF (2003) Novel therapeutic targets in Helicobacter pylori. Expert Opin Ther Targets 7:725–735

    Article  CAS  PubMed  Google Scholar 

  • Minkara MS, Ucisik MN, Weaver MN, Merz KM Jr (2014) Molecular dynamics study of Helicobacter pylori urease. J Chem Theory Comput 10:1852–1862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mobley HLT, Mendz GL, Hazell SL (2001) Helicobacter pylori: physiology and genetics. Washington (DC), ASM Press

  • Noe MC, Peakman M-C (2017) Drug discovery technologies: Current and future trends. In: S. Chackalamannil, D. Rotella, S.E. Ward (eds) Comprehensive Medicinal Chemistry III, Elsevier, Oxford, pp. 1–32

  • Repetto MG, Llesuy SF (2002) Antioxidant properties of natural compounds used in popular medicine for gastric ulcers. Brazilian J Med Biol Res 35:523–534

    Article  CAS  Google Scholar 

  • Roszczenko-Jasińska P, Wojtyś MI, Jagusztyn-Krynicka EK et al (2018) New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. Future Microbiol 3:435–444

    Google Scholar 

  • Roszczenko-Jasińska P, Wojtyś MI, Jagusztyn-Krynicka EK (2020) Helicobacter pylori treatment in the post-antibiotics era—searching for new drug targets. Appl Microbiol Biotechnol 104:9891–9905

    Article  PubMed  PubMed Central  Google Scholar 

  • Santhosh S, Mathew PT (2008) Preparation and properties of glucosamine and carboxymethylchitin from shrimp shell. J Appl Polym Sci 107:280–285

    Article  CAS  Google Scholar 

  • Santhosh S, Anandan R, Sini TK et al (2005) Biochemical studies on the antiulcer effect of glucosamine on antioxidant defense status in experimentally induced peptic ulcer in rats. J Clin Biochem Nutr 37:61–66

    Article  CAS  Google Scholar 

  • Takeuchi H, Trang VT, Morimoto N et al (2014) Natural products and food components with anti-helicobacter pylori activities. World J Gastroenterol WJG 20:8971

    PubMed  Google Scholar 

  • Tarsia C, Danielli A, Florini F et al (2018) Targeting Helicobacter pylori urease activity and maturation: In-cell high-throughput approach for drug discovery. Biochim Biophys Acta (BBA)-General Subj 1862:2245–2253

    Article  CAS  Google Scholar 

  • Uprety B, Chandran R, Arderne C, Abrahamse H (2022) Anticancer activity of urease mimetic cobalt (III) complexes on A549-lung cancer cells: targeting the acidic microenvironment. Pharmaceutics 14:211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Valenzuela-Valderrama M, Cerda-Opazo P, Backert S et al (2019) The helicobacter pylori urease virulence factor is required for the induction of hypoxia-induced factor-1α in gastric cells. Cancers (Basel) 11:799

    Article  PubMed  Google Scholar 

  • Zhang H, Jiang Q, Gong G et al (2023) Alpinetin: anti-human gastric cancer potential and urease inhibition activity in vitro. Arch Med Sci AMS 19:1479

    Article  PubMed  Google Scholar 

Download references

Funding

This study did not receive any support from any institution or supporting agency.

Author information

Authors and Affiliations

  1. Department of Animal Production, College of Agriculture, Al-Qasim Green University, 8, Al-Qasim, Babil, 51013, Iraq

    Mohammed Baqur S. Al-Shuhaib

  2. Department of Clinical Laboratory Sciences, College of Pharmacy, University of Babylon, Hillah, Babil, 51001, Iraq

    Hayder O. Hashim

  3. College of Medicine, University of Warith Al-Anbiyaa, Karbala, 56001, Iraq

    Jafar M. B. Al-Shuhaib

Authors
  1. Mohammed Baqur S. Al-Shuhaib
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hayder O. Hashim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jafar M. B. Al-Shuhaib
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MBSA: Conceptualization, Methodology. Software, Writing–Original draft preparation. HOH; Software, Data curation, JMBA; Data curation, Reviewing and Editing. All authors approved the final draft of the manuscript.

Corresponding author

Correspondence to Mohammed Baqur S. Al-Shuhaib.

Ethics declarations

Conflict of interest

None of the authors have any financial or personal relationships that could inappropriately influence or bias the content of the paper.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 18.1 kb)

Supplementary material 2 (DOCX 15.9 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Al-Shuhaib, M.B.S., Hashim, H.O. & Al-Shuhaib, J.M.B. D-Glucosamine is a Potential Urease Inhibitor from Middle Eastern Medicinal Plants for Combatting Helicobacter Pylori Infections; a Molecular Docking and Simulation Approach. Biochem Genet (2024). https://doi.org/10.1007/s10528-024-10709-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10528-024-10709-5

Keywords

Search

Navigation