Tetrasiklin Antibiyotikleri ve Bromelain Enzimi Arasındaki Etkileşimlerin Kenetleme Araçları Kullanılarak İncelenmesi

Year 2023, , 2986 - 2996, 01.12.2023

Gülgün Aylaz

https://doi.org/10.21597/jist.1306563

Abstract

Ananas sapından ekstrakte edilen bromelain, farklı amaçlar için kullanılan kompleks bir enzimdir. Bromelain takviyeleri genellikle sindirimi kolaylaştırmak, dolaşım sistemini iyileştirmek ve ağrı kesici özelliğinden dolayı artrit semptomlarını hafifletmek için kullanılır. Ancak antibiyotik kullanımı veya kanama riski olan bazı durumlarda bromelain kullanımı veya doğrudan ananas tüketimi sınırlandırılmalıdır. Bu amaçla antibiyotik bromelain etkileşiminin hangi mekanizma ile gerçekleştiğini göstermek amacıyla bu çalışma yapılmıştır. İlk olarak UCSF Chimera görselleştirme programında bromelain molekülü ve demeklosiklin, minosiklin ve tetrasiklin antibiyotikleri hazırlanmıştır. Etkileşimler, Auto Dock Molecular Modeling Toolkit moleküler modelleme programında görüntülenmiştir. Bu etkileşimlerin serbest bağlanma enerjileri de Auto Dock'ta hesaplanmıştır. Moleküler modelleme sonuçlarına göre, bromelain ve demeklosiklin, minosiklin, tetrasiklin antibiyotikleri, hidrojen bağları ve hidrofobik etkileşimler ile etkileşime girmiştir. Bromelain ve antibiyotikler arasındaki bu etkileşimler, serbest bağlanma enerjisi hesaplamalarına dayalı olarak enerjisel olarak uygun bulunmuştur.

Keywords

Bromelain, Moleküler kenetleme, Demeklosiklin, Minosiklin, Tetrasiklin

Project Number

--

Investigation of Interactions Between Tetracycline Antibiotics and Bromelain Enzyme Using Docking Tools

Abstract

Bromelain, extracted from the stem of the pineapple, is a complex enzyme used for different purposes. Bromelain supplements are often used to facilitate digestion, improve the circulatory system and relieve arthritis symptoms due to its pain relief. However, in some cases where there is a risk of antibiotic use or bleeding, the use of bromelain or direct consumption of pineapple should be limited. For this purpose, this study was carried out to show the mechanism by which the antibiotic bromelain interaction occurs. Firstly, the bromelain molecule and demeclocycline, minocycline, and tetracycline antibiotics were prepared in the UCSF Chimera visualizing program. The interactions were monitored in the Auto Dock Molecular Modelling Toolkit molecular modeling program. The free binding energies of these interactions were also calculated in Auto Dock. According the molecular modelling results, bromelain and demeclocycline, minocycline, tetracycline antibiotics were interact with hydrogen bonds and hydrophobic interactions. These interactions between bromelain and antibiotics were energetically favorable based on free binding energy calculations.

Keywords

Bromelain, molecular docking, demeclocycline, minocycline, tetracycline

Supporting Institution

Çalışma için herhangi bir resmi yada özel kurum/şahıstan destek alınmamıştır.

Project Number

--

Thanks

--

References

• Allahverdiyeva, S., Yardım, Y. & Şentürk, Z. (2021). Electrooxidation of tetracycline antibiotic demeclocycline at unmodified boron-doped diamond electrode and its enhancement determination in surfactant-containing media. Talanta, 223, 121695.
• Angelette, A.L., Rando, L.L., Wadhwa, R.D., Barras, A.A., Delacroix, B.M., Talbot, N.C., Ahmadzadeh, S., Shekoohi, S., Cornett, E.M., Kaye, A.M., Kaye, A.D. (2022). Tetracycline-, Doxycycline-, Minocycline-Induced Pseudotumor Cerebri and Esophageal Perforation. Advances in Therapy, 40, 1366–1378.
• Aylaz, G. & Andac, M. (2022). Affinity Recognition Based Gravimetric Nanosensor for Equilin Detection. Chemosensors, 10 (172), 1-21.
• Azarkan, M., Maquoi, E., Delbrassine, F., Herman, R., Rabet, N., Esposito, R.C., Charlie, P. & Kerff, F. (2020). Structures of the free and inhibitors‑bound forms of bromelain and ananain from Ananas comosus stem and in vitro study of their cytotoxicity. Scientific Reports, 10, 19570.
• Banihashemrad, S.A., Nasrabadi, N., Rajabi, O., Kanafi, A.R., Taher, M. (2020). Impact of Bromelain on wound healing and complications after periodontal surgery. Arch Pharma Pract, 11(S1), 38-41.
• Bharadwaj, S., Lee, K.E., Dwivedib, V.D., Kanga, S.G. (2020). Computational insights into tetracyclines as inhibitors against SARS-CoV-2 Mpro via combinatorial molecular simulation calculations. Life Sciences, 257, 118080.
• Chakraborty, A.J., Mitra, S., Tallei, T.E., Tareq, A.M., Nainu, F., Cicia, D., Dhama, K., Emran, T., Gandara, J.S., Capasso, R. (2021). Bromelain a Potential Bioactive Compound: A Comprehensive Overview from a Pharmacological Perspective. Life, 11, 317.
• Chisci, G. & Fredianelli, L. (2022). Therapeutic Efficacy of Bromelain in Alveolar Ridge Preservation. Antibiotics, 11, 1542.
• Dighe, N.S., Pattan, S.R., Merekar, A.N., Laware, R.B., Bhawar, S.B., Nirmal, S.N., Gaware, V.M., Hole1, M.B., Musmade, D.S. (2010). Bromelain A Wonder Supplement: A Review. Pharmacologyonline, 1, 11-18.
• Elton, D.C., Boukouvalas, Z., Fuge, M.D. & Chung, P.W. (2019). Deep learning for molecular design-a review of the state of the art. Molecular Systems Design & Engineering, 4, 828-849.
• Gupta, A.A., Kambala, R., Bhola, N. & Jadhav, A. (2022). Comparative efficacy of bromelain and aceclofenac in limiting post-operative inflammatory sequelae in surgical removal of lower impacted third molar: a randomized controlled, triple blind clinical trial. Journal of Dental Anesthesia and Pain Medicine, 22(1), 29-37.
• Hu, X., Zhang, Y., Chen, Z., Gao, Y., Teppen, B., Boyd, S.A., Zhang, W., Tiedje, J.M., Li H. (2023). Tetracycline accumulation in biofilms enhances the selection pressure on Escherichia coli for expression of antibiotic resistance. Science of the Total Environment, 857, 159441.
• Jancic, U. & Gorgieva, S. (2022). Bromelain and Nisin: The Natural Antimicrobials with High Potential in Biomedicine. Pharmaceutics, 14(76), 1-39.
• Ji, S., Gavande, P.V., Choudhury, B. & Goyal, A. (2023). Computational design and structure dynamics analysis of bifunctional chimera of endoxylanase from Clostridium thermocellum and xylosidase from Bacteroides ovatus. 3 Biotech, 13(59), 2-19.
• Jones, D., Kim, H., Zhang, X., Zemla, A., Stevenson, G., Bennett, W.F.D., Kirshner, D., Wong, S.E., Lightstone, F.C. & Allen, J.E. (2021). Improved Protein−Ligand Binding Affinity Prediction with Structure-Based Deep Fusion Inference. ACS Journal of Chemical Information and Modeling, 61, 1583-1592.
• Juhi, Baghel, N., Singh, R., Sharma, P. (2023). A Systematic Review of Toxicity of Antibiotics Used in the Treatment of STIs with Special Emphasis on Web-based Toxicity Analyzing Software. Asian Journal of Biological and Life Sciences, 12, 1.
• Ke, K., Pillai, K., Mekkawy, A.H. Akhter, J., Badar, S., Valle, S.J., Morris, D.L. (2022). Physical and chemical factors affecting the loading and release of bromelain from DC beads. American Journal of Translational Research, 14(10), 7135-7146.
• Kılıç, S., Andaç, M. & Denizli, A. (2021). Bindingmodes of cibacron blue with albumin in affinity chromatography using docking tools. International Journal of Biological Macromolecules, 183, 110-118.
• Kumar, P.K., Jha, I., Sindhu, A., Venkatesu, P., Bahadur, I. & Ebenso, E.E. (2020). Experimental and molecular docking studies in understanding the biomolecular interactions between stem bromelain and imidazolium based ionic liquids. Journal of Molecular Liquids, 297, 111785.
• Kumar, R., Kumar, R., Sharma, N., Khurana, N., Singh, S.K., Satija, S., Mehta, M. & Vyas, M. (2022). Pharmacological evaluation of bromelain in mouse model of Alzheimer’s disease. Neurotoxicology, 2022, 90, 19-34.
• LaPlante, K.L., Dhand, A., Wright, K., Lauterio, M. (2022). Re-establishing the utility of tetracycline class antibiotics for current challenges with antibiotic resistance. Annals of Medicine, 54:1, 1686-1700.
• Leichtweisa, J., Vieirab, Y., Weltera, N., Silvestria, S., Dottob, G.L., Carissimia, E. (2022). A review of the occurrence, disposal, determination, toxicity and remediation technologies of the tetracycline antibiotic. Process Safety and Environmental Protection, 160, 25–40.
• Liang, G., Zhao, J., Gao, Y., Xie, T., Zhen, J., Pan, L., Gong, W. (2023). Application and evaluation of molecular docking for aptamer and small molecular interaction - A case study with tetracycline antibiotics. Talanta, 266, 124942.
• Li, J., Fu, A. & Zhang, L. (2019). An Overview of Scoring Functions Used for Protein–Ligand Interactions in Molecular Docking. Interdisciplinary Sciences: Computational Life Sciences, 11, 320-328.
• Li, N., Zhou, L., Jin, X., Owens, G. & Chen, Z. (2019). Simultaneous removal of tetracycline and oxytetracycline antibiotics from wastewater using a ZIF-8 metal organic-framework. Journal of Hazardous Materials, 366, 563-572.
• Li, Z.H., Yuan, L., Wang, L., Liu, Q., Sheng, G.P. (2022). Coexistence of silver ion and tetracycline at environmentally relevant concentrations greatly enhanced antibiotic resistance gene development in activated sludge bioreactor. Journal of Hazardous Materials, 423, 127088.
• Maher, H.M., Almomen, A., Alzoman, N.Z., Shehata, S.M. & Alanazi, A.A. (2021). Development and validation of UPLC–MS/MS method for thesimultaneous quantification of anaplastic lymphoma kinase inhibitors, alectinib, ceritinib, and crizotinib in Wistar rat plasma withapplication to bromelain-induced pharma cokinetic interaction. Journal of Pharmaceutical and Biomedical Analysis, 204, 114276.
• Maheshwari, D.G., Shah, J.S., Shah, D.B., Patel, P.K. & Singh, Y.R. (2023). Emerging trends in extraction and analytical techniques for bromelain. Journal of Liqui Chromatography & Related Technologies, 45(9), 107-119.
• Mameli, A., Natoli, V. & Casu, C. (2021). Bromelain: an Overview of Applications in Medicine and Dentistry. Biointerface Research in Applied Chemistry, 11(1), 8165-8170.
• Mauer, H.R. (2001). Bromelain: biochemistry, pharmacology and medical use. Cellular and Molecular Life Sciences, 58, 1234–1245.
• Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S. & Olson, A.J. (2009). AutoDock4 and AutoDockTools4: Automated Docking with Selective Receptor Flexibility. Software News and Updates, 30, 2785-2791.
• Olivera, O.V., Rocha, G.B., Paluch, A.S. & Costa, L.T. (2021). Repurposing approved drugs as inhibitors of SARSCoV- 2 S-protein from molecular modeling and virtual screening. Journal of Biomolecular Structure and Dynamics, 39 (11), 3924-3933.
• Olshannikova, S.S., Malykhina, N.V., Lavlinskaya, M.S., Sorokin, A.V., Yudin, N.E., Vyshkvorkina, Y.M., Lukin, A.N., Holyavka, M.G., Artyukhov, V.G. (2022). Novel Immobilized Biocatalysts Based on Cysteine Proteases Bound to 2-(4-Acetamido-2-sulfanilamide) Chitosan and Research on Their Structural Features. Polymers,14, 3223.
• Pang, W.C., Ramli, A.M. & Hamid, A.A.A. (2020). Comparative modelling studies of fruit bromelain using molecular dynamics simulation. Journal of Molecular Modeling, 26,142.
• Pankovaa, S. M., Holyavkaa, M.G., Kondrat’evd, M.S., Vyshkvorkinae, Y.M., Lukina, A.N., Artyukhova, V.G. (2022). A Chitosan Matrix as a Photomodulator for Bromelain. Biology Bulletin, 49, 11, 2126–2133.
• Pavan, R., Jain, S., Shraddha, Kumar, A. (2012). Properties and Therapeutic Application of Bromelain: A Review. Biotechnology Research International, 976203, 6 pages.
• Pereira, I.C., Satiro, E.E., Torres, L.R.O., Silva, F.C.C., Sousa, J.M.C. & Leal, F.L.T. (2023). Bromelain supplementation and inflammatory markers: a systematic review of clinical trials. Clinical Nutrition Espen, 55, 116-127.
• Petkovic, H., Cullum, J., Hranueli, D., Hunter, I. S., Concha, N., Pigac, J., Thamchaipenet, A., Vujaklija, D. & Long, P. F. (2006). Genetics of Streptomyces rimosus, the Oxytetracycline Producer. Microbiology And Molecular Biology Reviews, 704-728.
• Pettersen E.F., Goddard, T.D., Huang, C.C., Couch, G.S., Greenblastt, D.M., Meng, E.C. & Ferrin, T.E. (2004). UCSF Chimera—A Visualization System for Exploratory Research and Analysis. Wiley InterScience, 25, 1605-1612.
• Romm, A., Burgess, I., Winston, D., Zick, S.M., Crawford, A.MQ. (2010). Conditions of the Reproductive Organs. General Gynecologic and Menstrual Health Concerns, Chapter 7, 211-255.
• Sabe, V.T., Ntombela, T., Jhamba, L.A., Maguire, G.E.M., Govender, T., Naicker, T. & Kruger, H.G. (2021). Current trends in computer aided drug design and a highlight of drugs discovered via computational techniques: A review. European Journal of Medicinal Chemistry, 224, 113705.
• Sharma, M., Chaudhary, D. & Pharm, M. (2022). In vitro and in vivo implications of rationally designed bromelain laden core-shell hybrid solid lipid nanoparticles for oral administration in thrombosis management. Nanomedicine: Nanotechnology, Biology, and Medicine, 42, 102543.
• Salha, D., Andaç, M. & Denizli, A. (2020). Molecular docking of metal ion immobilized ligands to proteins in affinity chromatography. Journal of Molecular Recognition, 34, e2875.
• Singh, T., Thapliyal, S., Bhatia, S., Singh, V., Singh, M., Singh, H., Kumar, A. & Mishra, A. (2022). Reconnoitering the transformative journey of minocycline from an antibiotic to an antiepileptic drug. Life Sciences, 293, 120346.
• Solis-Vasquez, L., Tillack, A.F., Martins, D.S., Koch, A., LeGrand, S. & Forli, S. (2022). Benchmarking the performance of irregular computations in AutoDock-GPU molecular docking. Parallel Computing, 109, 102861.
• Sorokin, A.V., Goncharova, S.S., Lavlinskaya, M.S., Holyavka, M.G., Faizullin, D.A., Zuev, Y.F., Kondratyev, M.S., Artyukhov, V.G. (2023). Complexation of Bromelain, Ficin, and Papain with the Graft Copolymer of Carboxymethyl Cellulose Sodium Salt and N-Vinylimidazole Enhances Enzyme Proteolytic Activity. International Journal of Molecular Sciences, 24, 11246.
• Wang, K.M., Zhou, L.X., Ji, K.F., Xu, S.N. & Wang, J.D. (2022). Evaluation of a modified internal circulation (MIC) anaerobic reactor for real antibiotic pharmaceutical wastewater treatment: Process performance, microbial community and antibiotic resistance genes evolutions. Journal of Water Process Engineering, 40, 102914.
• Wang, R., Fang, X., Lu, Y., Wang, S. (2003). The PDBbind Database: Collection of Binding Affinities for Protein-Ligand Complexes with Known Three-Dimensional Structures. Journal of Medicinal Chemistry, 47, 12, 2977-2980.
• Yang, S.Y. (2010). Pharmacophore modeling and applications in drug discovery: challenges and recent advances. Drug Discovery Today, 15, 11/12, 444-450.