Evaluation Of Antibacterial Potential Of Thiazole,Sulfonamide And Indole Derivatives Against Fima Of P.Gingivalis Using In Silico Molecular Docking And Admet Prediction
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Keywords
FimA , p.gingivalis , periodontitis , gingiva ,toxicity ,drugs
Abstract
Aim : The main aim of the study is to evaluate the antimicrobial potential of thiazole, sulfonamide and indole derivatives against FimA of P.gingivalis using molecular docking techniques.
Introduction: Periodontal disease is a chronic inflammatory disease of the supporting structure of the teeth that causes gum inflammation, periodontal tissue degeneration, almost complete loss of alveolar bone, and eventually tooth exfoliation. The numerous interactions between P. gingivalis and the host immune system, together with its numerous virulence factors, such as fimbriae, cysteine proteinases, hemagglutinins, and lipopolysaccharide (LPS), clearly indicate its potency as a pathogen.
Materials and method : Utilizing ChemDraw and Chem3D software, the 2D structures (mol) of the thiazole, sulphonamide, and indole compounds (NN1-NN9) were created. The selected molecules were handled quantum mechanically by applying the DFT approach using the Gaussian 09 programme suite at the Becke3-Lee-YangPar (B3LYP) level and the common 6-31G (d,p) basis set. In order to create a stable construction with the least amount of energy, all of the parameters were chosen during the optimization process.
Results and discussion : Red complex bacteria have a significant role in the aetiology of periodontitis, which is an illness with several factors. The more dangerous red complex bacteria are the last bacteria to colonize and cause the breakdown of the periodontium. So based on ADMET prediction compound 4 (NN4) can be used as a potential drug for further investigations by eliminating the hepatotoxicity alone.
Conclusion : In this study, molecular docking was used to determine that NN4 had superior properties to already approved clinical drugs in terms of inhibiting the activity of P. gingivalis and acting as an adjunct or substitute for antibiotics in the treatment of periodontitis.
References
144
2. Alwaeli AZJ (2018) Anaerobic bacteria associated with periodontitis. In: Oral microbiology in periodontitis. IntechOpen
3. Hajishengallis G (2015) Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol 15(1):30–44
4. Jia L, Han N, Du J, Guo L, Luo Z, Liu Y (2019) Pathogenesis of important virulence factors of Porphyromonas gingivalis via toll-like receptors.
Front Cell Infect Microbiol 9:262
5. Herath TDK, Darveau RP, Seneviratne CJ, Wang C-Y, Wang Y, Jin L (2013) Tetra-and pentaacylated lipid a structures of Porphyromonas gingivalis LPS differentially activate TLR4-mediated NF-κB signal transduction cas- cade and immuno-inflammatory response in human gingival fibroblasts. PLoS One 8(3):e58496
6. How KY, Song KP, Chan KG (2016) Porphyromonas gingivalis: an overview of periodontopathic pathogen below the gum line. Front Microbiol 7:53
7. Sharma A (2010) Virulence mechanisms of Tannerella forsythia. Periodon- tol 54(1):106
8. Jusko M, Potempa J, Mizgalska D, Bielecka E, Ksiazek M, Riesbeck K et al (2015) A metalloproteinase mirolysin of Tannerella forsythia inhibits all pathways of the complement system. J Immunol 195(5):2231–2240
9. Dashper SG, Seers CA, Tan KH, Reynolds EC (2011) Virulence factors of the oral spirochete Treponema denticola. J Dent Res 90(6):691–703
10. Spyrakis F, Cellini B, Bruno S, Benedetti P, Carosati E, Cruciani G et al (2014) Targeting cystalysin, a virulence factor of treponema denticola-supported periodontitis. ChemMedChem. 9(7):1501–1511
11. Huan Y, Kong Q, Mou H, Yi H (2020) Antimicrobial peptides: classifica- tion, design, application and research progress in multiple fields. Front Microbiol 11:2559
12. Mahlapuu M, Håkansson J, Ringstad L, Björn C (2016) Antimicrobial peptides: an emerging category of therapeutic agents. Front Cell Infect Microbiol 6:194
13. Jourdain M, Velard F, Pierrard L, Sergheraert J, Gangloff SC, Braux J (2019) Cationic antimicrobial peptides and periodontal physiopathology: a systematic review. J Periodontal Res 54(6):589–600
14. Dale BA, Krisanaprakornkit S (2001) Defensin antimicrobial peptides in the oral cavity. J Oral Pathol Med Rev Artic 30(6):321–327
15. Jiménez-García B, Pons C, Fernández-Recio J (2013) pyDockWEB: a web server for rigid-body protein–protein docking using electrostatics and desolvation scoring. Bioinformatics. 29(13):1698–1699
16. Weinberg A, Jin G, Sieg S, McCormick TS (2012) The yin and yang of human Beta-defensins in health and disease. Front Immunol 3:294
17. Dashper SG, Pan Y, Veith PD, Chen Y-Y, Toh ECY, Liu SW et al (2012) Lactoferrin inhibits Porphyromonas gingivalis proteinases and has sustained biofilm inhibitory activity. Antimicrob Agents Chemother 56(3):1548–1556
18. Wang HY, Liu JW, Li Q, Tan LS, Lin L, Pan YP (2018) A preliminary study on the effect of histatin 5 inhibiting Porphyromonas gingivalis and Fusobac- terium nucleatum co-aggregation. Zhonghua kou Qiang yi xue za zhi= Zhonghua Kouqiang Yixue Zazhi= Chinese J Stomatol 53(3):150–156
19. Olsen I, Potempa J (2014) Strategies for the inhibition of gingipains for the potential treatment of periodontitis and associated systemic diseases. J Oral Microbiol 6(1):24800
20. Sethi A, Joshi K, Sasikala K, Alvala M (2019) Molecular docking in modern drug discovery: principles and recent applications. Drug Discov Dev Adv 2:1–21
21. Azam SS, Abbasi SW (2013) Molecular docking studies for the identifi- cation of novel melatoninergic inhibitors for acetylserotonin-Ometh- yltransferase using different docking routines. Theor Biol Med Model 10(1):1–16
22. Lei J, Sun L, Huang S, Zhu C, Li P, He J et al (2019) The antimicrobial pep- tides and their potential clinical applications. Am J Transl Res 11(7):3919
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