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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Short Communication

In-silico Validation of the Proposed Treatment Strategy of Periodontitis

Author(s): Pooja Jain, Uzma Farooq, Lalit Mohan Nainwal, Mumtaz Alam, Naseef Punnoth Poonkuzhi, Mohamed Saheer Kuruniyan, Mohd. Aamir Mirza* and Zeenat Iqbal*

Volume 25, Issue 13, 2022

Published on: 22 April, 2022

Page: [2295 - 2313] Pages: 19

DOI: 10.2174/1386207325666220126102235

Price: $65

Abstract

Objective: The present study aims to assess a proposed treatment approach or therapy for periodontitis by using the in-silico technique. The proposed treatment strategy offers a singular vehicular system consisting of minocycline (antibiotic), celecoxib (selective COX-II inhibitor), doxycycline hyclate (matrix metalloproteinase inhibitor), and hydroxyapatite (osteogenic agent).

Material and Methods: Molecular docking studies of drugs were performed using Maestro version 9.4 software Schrödinger, and 3-Dimensional Crystallographic X-ray protein structures of targeted proteins were downloaded from RCSB protein data bank in .pdb file format. These agents were docked, and their affinities towards the receptors/protein/enzyme were calculated. Furthermore, their affinities were compared with the standard drug.

Results: The study suggests that minocycline and metronidazole possess equal affinity towards the RGPB and Inlj protein of P.gingivalis. Celecoxib, a well-known inhibitor of the COX-II enzyme, showed very high affinity. Selective inhibitor of MMP-8 possessed higher affinity than doxycycline, whereas CMT-3 showed equal affinity as doxycycline for MMP-13. Similarly, hydroxyapatite and simvastatin also showed a comparatively similar affinity for osteopontin receptor.

Conclusion: Based upon molecular docking results, it can be concluded that the proposed treatment strategy would be a suitable approach for periodontitis and all the selected therapeutic agents have potential similar to the standard drugs, thereby constituting a reliable system for periodontitis.

Keywords: Molecular docking, In-silico, affinity, periodontotherapy, minocycline, doxycycline, celecoxib, hydroxyapatite.

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[1]
Jain, P.; Dilnawaz, F.; Iqbal, Z. Insights into nanotools for dental interventions. In: Yata, V.K.; Ranjan, S.; Dasgupta, N.; Lichtfouse, E., Eds.;Nanopharmaceuticals: Principles and Applications; Springer International Publishing: New York, USA, 2020, Vol. 3, pp. 53-79.
[http://dx.doi.org/10.1007/978-3-030-47120-0_3]
[2]
Jain, P. Design and in vitro/in vivo evaluations of a multiple-drug-containing gingiva disc for periodontotherapy. RSC Advances, 2020, 10, 8530-8538.
[http://dx.doi.org/10.1039/C9RA09569A]
[3]
Gerits, E.; Verstraeten, N.; Michiels, J. New approaches to combat Porphyromonas gingivalis biofilms. J. Oral Microbiol., 2017, 9(1), 1300366.
[http://dx.doi.org/10.1080/20002297.2017.1300366] [PMID: 28473880]
[4]
Anarthe, R.; Mani, A.; Marawar, P. Host modulatory therapy: A novel approach in the periodontal therapy. ISOR J. Pharm., 2013, 3, 9-13.
[http://dx.doi.org/10.9790/3013-03410913]
[5]
Slots, J.; Ting, M. Systemic antibiotics in the treatment of periodontal disease. Periodontol. 2000, 2002, 28, 106-176.
[http://dx.doi.org/10.1034/j.1600-0757.2002.280106.x] [PMID: 12013339]
[6]
Jain, P.; Mirza, M.A.; Iqbal, Z.A. 4-D approach for amelioration of periodontitis. Med. Hypotheses, 2019, 133, 109392.
[http://dx.doi.org/10.1016/j.mehy.2019.109392] [PMID: 31521022]
[7]
Nakayama, K.; Kadowaki, T.; Okamoto, K.; Yamamoto, K. Construction and characterization of arginine-specific cysteine proteinase (Arg-gingipain)-deficient mutants of Porphyromonas gingivalis. Evidence for significant contribution of Arg-gingipain to virulence. J. Biol. Chem., 1995, 270(40), 23619-23626.
[http://dx.doi.org/10.1074/jbc.270.40.23619] [PMID: 7559528]
[8]
Sztukowska, M.N.; Dutton, L.C.; Delaney, C.; Ramsdale, M.; Ramage, G.; Jenkinson, H.F.; Nobbs, A.H.; Lamont, R.J. Community devel-opment between Porphyromonas gingivalis and Candida albicans mediated by InlJ and Als3. MBio, 2018, 9(2), e00202-e00218.
[http://dx.doi.org/10.1128/mBio.00202-18] [PMID: 29691333]
[9]
Cosgarea, R.; Heumann, C.; Juncar, R.; Tristiu, R.; Lascu, L.; Salvi, G.E.; Arweiler, N.B.; Sculean, A. One year results of a randomized controlled clinical study evaluating the effects of non-surgical periodontal therapy of chronic periodontitis in conjunction with three or seven days systemic administration of amoxicillin/metronidazole. PLoS One, 2017, 12(6), e0179592.
[http://dx.doi.org/10.1371/journal.pone.0179592] [PMID: 28662049]
[10]
Eickholz, P.; Koch, R.; Kocher, T.; Hoffmann, T.; Kim, T.S.; Meyle, J.; Kaner, D.; Schlagenhauf, U.; Harmsen, D.; Harks, I.; Ehmke, B. Clinical benefits of systemic amoxicillin/metronidazole may depend on periodontitis severity and patients’ age: An exploratory sub-analysis of the ABPARO trial. J. Clin. Periodontol., 2019, 46(4), 491-501.
[http://dx.doi.org/10.1111/jcpe.13096] [PMID: 30825384]
[11]
Dahlen, G.; Preus, H.R. Low antibiotic resistance among anaerobic Gram-negative bacteria in periodontitis 5 years following metronida-zole therapy. Anaerobe, 2017, 43, 94-98.
[http://dx.doi.org/10.1016/j.anaerobe.2016.12.009] [PMID: 27988390]
[12]
Gemmell, E.; Marshall, R.I.; Seymour, G.J. Cytokines and prostaglandins in immune homeostasis and tissue destruction in periodontal disease. Periodontol. 2000, 1997, 14, 112-143.
[http://dx.doi.org/10.1111/j.1600-0757.1997.tb00194.x] [PMID: 9567968]
[13]
Preshaw, P.M.; Hefti, A.F.; Jepsen, S.; Etienne, D.; Walker, C.; Bradshaw, M.H. Subantimicrobial dose doxycycline as adjunctive treatment for periodontitis. A review. J. Clin. Periodontol., 2004, 31(9), 697-707.
[http://dx.doi.org/10.1111/j.1600-051X.2004.00558.x] [PMID: 15312090]
[14]
Zhang, J. Research advances and clinical practice in periodontics: Bridging the gap 39. Res. Advan. Periodontal Diagn., 2006, 26, 38.
[15]
Golub, L.M.; Ryan, M.E.; Williams, R.C. Modulation of the host response in the treatment of periodontitis. Dent. Today, 1998, 17(10), 102-106, 108-109.
[PMID: 10752438]
[16]
Golub, L.M.; Sorsa, T.; Lee, H.M.; Ciancio, S.; Sorbi, D.; Ramamurthy, N.S.; Gruber, B.; Salo, T.; Konttinen, Y.T. Doxycycline inhibits neutrophil (PMN)-type matrix metalloproteinases in human adult periodontitis gingiva. J. Clin. Periodontol., 1995, 22(2), 100-109.
[http://dx.doi.org/10.1111/j.1600-051X.1995.tb00120.x] [PMID: 7775665]
[17]
Ryan, M.; Lee, H.M.; Sorsa, T. Effects of short-term COL-3 on local biomarkers of periodontitis. J. Dent. Res., 2008, 87 Abstract # 0040.
[18]
Golub, L.M.; Lee, H.M. Periodontal therapeutics: Current host-modulation agents and future directions. Periodontol. 2000, 2020, 82(1), 186-204.
[http://dx.doi.org/10.1111/prd.12315] [PMID: 31850625]
[19]
Singh, A.; Gill, G.; Kaur, H.; Amhmed, M.; Jakhu, H. Role of osteopontin in bone remodeling and orthodontic tooth movement: A review. Prog. Orthod., 2018, 19(1), 18.
[http://dx.doi.org/10.1186/s40510-018-0216-2] [PMID: 29938297]
[20]
Jensen, T.; Baas, J.; Dolathshahi-Pirouz, A.; Jacobsen, T.; Singh, G.; Nygaard, J.V.; Foss, M.; Bechtold, J.; Bünger, C.; Besenbacher, F.; Søballe, K. Osteopontin functionalization of hydroxyapatite nanoparticles in a PDLLA matrix promotes bone formation. J. Biomed. Mater. Res. A, 2011, 99(1), 94-101.
[http://dx.doi.org/10.1002/jbm.a.33166] [PMID: 21800419]
[21]
Hunter, G.K. Role of osteopontin in modulation of hydroxyapatite formation. Calcif. Tissue Int., 2013, 93(4), 348-354.
[http://dx.doi.org/10.1007/s00223-013-9698-6] [PMID: 23334303]
[22]
Chauhan, A.S.; Maria, A.; Managutti, A. Efficacy of simvastatin in bone regeneration after surgical removal of mandibular third molars: A clinical pilot study. J. Maxillofac. Oral Surg., 2015, 14(3), 578-585.
[http://dx.doi.org/10.1007/s12663-014-0697-6] [PMID: 26225047]
[23]
Ding, D.; Lichtenwalter, K.; Pi, H.; Mobashery, S.; Chang, M. Characterization of a selective inhibitor for matrix metalloproteinase-8 (MMP-8). MedChemComm, 2014, 5, 1381-1383.
[http://dx.doi.org/10.1039/C4MD00172A]

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