Evaluation of antimicrobial potential of oxazole compounds against Mfa1 virulence factor of Porphyromonas gingivalis using In silico molecular docking and ADMET predictions

Main Article Content

Navya Khanna
Parkavi Arumugam
Rajalakshmanan Eswaramoorthy

Keywords

Periodontitis, Porphyromonas gingivalis, Molecular docking, In silico analysis, drug development

Abstract

Introduction: A chronic inflammatory condition called periodontitis affects around half of adult Indians. One of the main events in the beginning and progression of periodontal disease is the colonisation of the oral cavity by the Gram-negative bacterial pathogen Porphyromonas gingivalis. Throughout the progression of the illness, P. gingivalis interacts with host cells and other bacteria through adhesive surface features known as fimbriae (pili). A new method that includes the proteolytic digestion of lipidated precursor subunits and their subsequent polymerization on the bacterial surface is used to build the P. gingivalis fimbriae. The P. gingivalis fimbriae are promising targets for anti-infective treatments to prevent or cure periodontal disease because of their extracellular assembly process and key roles in pathogenesis.
Aim: To identify potiential inhibitors of Mfa1 a virulence factor of P. gingivalis
Materials and methods: The structure of Mfa1 was predicted by the SWISS-MODEL web server and the structure was evaluated by different web tools. The structure of virulence factor of Porphyromonas gingivalis was drawn using Chem3D ultra 11.0 software. The structure of important protein virulence factors of red complex bacteria of periodontitis was determined by the SWISS-MODEL web server. The interaction study between oxazole compound and virulence factors was carried out by molecular docking using Auto dock version 4.0 software and pyDock WEB server.
Results & Discussion: The selected ligands show better interactions with the model led protein within the binding sites. Ligands NV1-4 and NV6 obey Lipinski’s rule of 5 with low toxicity profile and give better interaction score. These ligands can be validated and can be used as it has better absorption and no cytotoxicity 


Conclusion: After comparing all the ligands with each other, we can conclude that NV6 could be a potential drug inhibitor against Mfa1 in P. gingivalis in periodontitis, owing to its high LD50, inactive carcinogenic, mutagenic and immunogenic effect. It also had high hydrogen bond forming capacity.

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References

1. Alaei SR, Park JH, Walker SG, Thanassi DG. Peptide-Based Inhibitors of Fimbrial Biogenesis in Porphyromonas gingivalis. Infect Immun [Internet]. 2019 Mar;87(3). Available from: http://dx.doi.org/10.1128/IAI.00750-18
2. Deresa DA, Abdissa Z, Gurmessa GT, Abdissa N. Molecular docking analysis of chemical constituents from the stem barks of podocarpus falcatus and evaluation for antibacterial activity [Internet]. Research Square. 2022. Available from: https://www.researchsquare.com/article/rs-1505415/latest.pdf
3. Machtei EE, Hausmann E, Dunford R, Grossi S, Ho A, Davis G, et al. Longitudinal study of predictive factors for periodontal disease and tooth loss. J Clin Periodontol. 1999 Jun;26(6):374–80.
4. Noack B, Genco RJ, Trevisan M, Grossi S, Zambon JJ, De Nardin E. Periodontal infections contribute to elevated systemic C-reactive protein level. J Periodontol. 2001 Sep;72(9):1221–7.
5. Roky MK. Identification and structural characterization functional motifs in the Porphyromonas gingivalis MFA1 short fimbria [Internet]. University of Louisville; 2020 [cited 2023 May 5]. Available from: https://ir.library.louisville.edu/etd/3517/
6. Sahilu R, Eswaramoorthy R, Mulugeta E, Dekebo A. Synthesis, DFT analysis, dyeing potential and evaluation of antibacterial activities of azo dye derivatives combined with in-silico molecular docking and ADMET predictions. J Mol Struct. 2022 Oct 5;1265:133279.
7. Sethi A, Joshi K, Sasikala K. Molecular docking in modern drug discovery: Principles and recent applications. Drug Discovery Dev [Internet]. 2019; Available from: https://books.google.com/books?hl=en&lr=&id=3XH8DwAAQBAJ&oi=fnd&pg=PA27&dq=Sethi+A,+Joshi+K,+Sasikala+K,+Alvala+M.+Molecular+docking+in+modern+drug+discovery:+Principles+and+recent+applications.+Drug+discovery+and+development-new+advances.+2019+Jul+2%3B2:1-21.&ots=RsjiHs4hDZ&sig=0QIWc8YkYUlJifMPOh2TYctHWtw
8. Venkata Subbiah H, Ramesh Babu P, Subbiah U. In silico targeting of red complex bacteria virulence factors of periodontitis with β-defensin 1. J Genet Eng Biotechnol. 2022 Apr 19;20(1):59.
9. Neelakantan P, Subbarao C, Ahuja R, Subbarao CV, Gutmann JL. Cone-beam computed tomography study of root and canal morphology of maxillary first and second molars in an Indian population. J Endod. 2010 Oct;36(10):1622–7.
10. Marickar RF, Geetha RV, Neelakantan P. Efficacy of contemporary and novel Intracanal medicaments against enterococcus faecalis. J Clin Pediatr Dent. 2014 Autumn;39(1):47–50.
11. Aldhuwayhi S, Mallineni SK, Sakhamuri S, Thakare AA, Mallineni S, Sajja R, et al. Covid-19 Knowledge and Perceptions Among Dental Specialists: A Cross-Sectional Online Questionnaire Survey. Risk Manag Healthc Policy. 2021 Jul 7;14:2851–61.
12. Markov A, Thangavelu L, Aravindhan S, Zekiy AO, Jarahian M, Chartrand MS, et al. Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders. Stem Cell Res Ther. 2021 Mar 18;12(1):192.
13. Sheriff K, Santhanam A. Knowledge and Awareness towards Oral Biopsy among Students of Saveetha Dental College. J Pharm Res [Internet]. 2018; Available from: https://www.indianjournals.com/ijor.aspx?target=ijor:rjpt&volume=11&issue=2&article=023
14. Jayaraj G, Ramani P, Sherlin HJ, Premkumar P. Inter-observer agreement in grading oral epithelial dysplasia–A systematic review. Journal of Oral and [Internet]. 2015; Available from: https://www.sciencedirect.com/science/article/pii/S2212555814000118
15. Dua K, Wadhwa R, Singhvi G, Rapalli V, Shukla SD, Shastri MD, et al. The potential of siRNA based drug delivery in respiratory disorders: Recent advances and progress. Drug Dev Res. 2019 Sep;80(6):714–30.
16. Gan H, Zhang Y, Zhou Q, Zheng L, Xie X, Veeraraghavan VP, et al. Zingerone induced caspase‐dependent apoptosis in MCF‐7 cells and prevents 7,12‐dimethylbenz(a)anthracene‐induced mammary carcinogenesis in experimental rats. J Biochem Mol Toxicol [Internet]. 2019 Oct;33(10). Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/jbt.22387