Bromukonazol’ ün Moleküler Etkileşim Mekanizmasının DFT ve Moleküler Kenetleme Yöntemleri İle Açıklanması

Year 2023, Volume: 27 Issue: 2, 266 - 272, 25.08.2023

Neslihan Kaya Kınaytürk

Abstract

İnsanlar için kanserojen potansiyeli yüksek olan Bromukonazol fungisitinin kuantum kimyasal hesaplamaları yapılarak yapı karakterizasyonunun aydınlatılmasının yanı sıra DNA proteini (PDB ID: 1BNA) ile moleküler kenetleme analizi yapıldı. Yoğunluk Fonksiyonel Teorisi (DFT) yöntemi B3LYP fonksiyoneli ve aug-ccpVDZ temel seti kullanılarak Gaussian09 programında optimize edildi. Zamana bağlı DFT (TD-DFT) yöntemi ile HOMO, LUMO enerjileri hesaplandı. Protein veri bankasından 1BNA proteinin kristal yapısı *.pdb formatında temin edildi ve ligandın optimize edilmiş geometrisi kullanılarak ligand ile proteinin etkileşimi AutoDock Vina programında analiz edildi. Moleküler kenetlenme çalışmaları sonucu, ligand-protein bağlanma enerjileri, ligand-protein arasında oluşabilecek hidrojen bağ bölgeleri ve sayısı tespit edilerek moleküler etkileşim mekanizması açıklanmıştır.

Keywords

DFT, Moleküler Kenetlenme, Bromukanazol, HOMO-LUMO

Supporting Institution

-

Project Number

-

Thanks

-

References

• [1] Zubrod, J., Bundschuh, M., Arts, G., Brühl, C., Imfeld, G., Knabel, A., Payraudeau, S., Rasmussen, J., Rohr, J., Scharmüller, A., Smalling, K., Stehle, S., Schulz, R., Schafer, R. 2049. Fungicides: An Overlooked Pesticide Class, Environmental Science & Technology, 53(7), 3347-3365.
• [2] Lefrancq, M., Imfeld, G., Payraudeau, S., Millet , M.2013. Kresoxim methyl deposition, drift and runoff in a vineyard catchment, Science of the Total Environment, 442, 503-508.
• [3] EFSA. 2010. Conclusion on the peer review of the pesticide risk assessment of the active substance bromuconazole, European Food Safety Authority (EFSA), 8(8), 1704-1785.
• [4] Mazur, C., Kenneke, J., Tebes-Stevens, C., Okino, M., Lipscomb, J. 2007. In Vitro Metabolism of the Fungicide and Environmental Contaminant trans-bromuconazole and Implications for Risk Assessment, Journal of Toxicology and Environmental Health, Part A, 70, 1241-1250.
• [5] Abdelhadya, D., El-magd, M. A., Elbialy, Z. Saleh, A. 2017. Bromuconazole-induced hepatotoxicity is accompanied by upregulation of PXR/CYP3A1 and downregulation of CAR/CYP2B1 gene expression. Toxicology Mechanisms and Methods, 27(7), 544-550.
• [6] Saadaoui, H., Boujelbane, F., Bui Ha, M., Mzoughi, N. 2022. Performance and degradation pathways of bromuconazole by gamma Şekil 4. Bromukanazol ile 1BNA proteinin (a) en iyi bağlanma ve aktif yerleşme pozu (b) rezidülere bağlanma etkileşimlerinin iki boyutlu görünümü radiation in aqueous solutions. Process Safety and Environmental Protection, 164, 299-308
• [7] Rjiba Touati, K., Hamdi, H., Mnassri, A., Guedri, Y., Mokni, M., Abid, S. 2022. Bromuconazole caused genotoxicity and hepatic and renal damage via oxidative stress process in Wistar rats. Environmental Science and Pollution Research, 29, 14111-14120.
• [8] Rjiba-Touati, K., Ayed-Boussema, I., Hamdi, H. Azzebi, A., Abid, S. 2022. Bromuconazole fungicide induces cell cycle arrest and apoptotic cell death in cultured human colon carcinoma cells (HCT116) via oxidative stress process, Biomarkers, 27(7), 659-670.
• [9] Qanungo, K., Thakur, A. 2022. An EQC Level I study of environmental partitioning of Bromuconazole, Materials Today: Proceedings, 64(4), 932-936.
• [10] Osman, A., El-Shama, S., Osman, A., El-Hameed, A. 2011. Toxicological and Pathological Evaluation of Prolonged Bromuconazole Fungicide Exposure in Male Rats, The Medical Journal of Cairo University, 79(1), 555-564.
• [11] Wu, S., Ji, X., Wang, J., Wu, H., Han, J., Zhang, H., Xu, J., Qian, M. 2021. Fungicide bromuconazole has the potential to induce hepatotoxicity at the physiological, metabolomic and transcriptomic levels in rats, Environmental Pollution, 280, . 116940
• [12] Qin, Z., Wang, W., Weng, Y., Bao, Z., Yang, G., Jin, Y. 2022. Bromuconazole exposure induces cardiotoxicity and lipid transport disorder in larval zebrafish, Comparative Biochemistry and Physiology, Part C, 262, 109451.
• [13] Özgen, A., Ünlü, N. 2022. Moleküler Kenetleme (Docking) Yöntemi ile Bakteriyel Bir Sinyal Kompleksi ve Peonidin Molekülü Etkileşiminin İncelenmesi, Fırat Üniversitesi Fen Bilimleri. Dergisi, 34(2), pp. 201-206.
• [14] Frisch, M.J., Trucks, G.W., Schlegel, H.B., Suzerain, G.E., Robb, M.A., Cheeseman Jr., J.R., Montgomery, J.A., Vreven, T., Kudin, K.N., Burant, J.C., Millam, J.M., Iyengar, S.S., Tomasi, J., Barone, V., Mennucci, B., Cossi, M., Scalmani, G., Rega, N., Petersson, G.A., Nakat, H. 2003. Gaussian 09.
• [15] G. Zhurko ve D. Zhurko, Chemcraft program, Academic version 1.8, 2009.
• [16] Dennington, R., Keith, T. A., Millam, J. M. 2009. GaussView, Revision 5.0. Semichem. Inc., Shawnee Mission, KS..
• [17] https://www.rcsb.org. rcsb pdb. (erişim tarihi 20.10. 2022)
• [18] Lindstrom, W., Morris, G., Weber, C., Huey, 2008. Using AutoDock 4 for Virtual Screening.
• [19] https://www.3ds.com/productsservices/BIOVIA/products/molecularmodeling-simulation/BIOVIA-discoverystudio/visualization.
• [20] Cox, E. 1958. Crystal Structure of Benzene, Revıews Of Modern Physıcs, 30(1), 159-162.
• [21] Çelik, S., Akyuz, S., Ozel, A. 2022. Vibrational spectroscopic characterization and structural investigations , of Cepharanthine, a natural alkaloid. Journal of Molecular Structure, 1258, 132693.
• [22] Celik, S., Akyuz, S., Ozel, A. 2022. Molecular modeling, DFT quantum chemical analysis, and molecular docking on edotecarin, an indolocarbazole anticancer agent, Molecular Crystals and Liquid Crystals, 1-23.
• [23] Luo, J.X., Yang, C.l. 2006. Study on Preparation and Crystal Structure of cis-Propiconazole, Chinese Journal of Pesticide Science, 8(1),20-24.
• [24] Oturak, H., Kaya Kınaytürk, N., Çırak, Ç. 2018. Experimental and Theoretical Spectral (FT-IR, Raman, NMR, UV-Vis and NLO)Analysis of a potential antitumor drug: 1-Methyl-6-Nitro-1HBenzimidazole, Spectroscopy and Spectral Analysis, 38(6), 1963.
• [25] Kaya Kınaytürk, N., Oturak, H. 2016. Identification of Structural and Spectral Features of 2-Amino4-Chlorobenzoic Acid and 4-Amino 2-Chlorobenzoic Acid:A Comparative Experimental and DFT Study, Acta Physıca Polonıca A, 130(1), 276-281.
• [26] Demaison, J., Margules, L., Boggs, J. 2003. The Equilibrium C–Cl, C–Br, and C–I Bond Lengths from Ab Initio Calculations, Microwave and Infrared Spectroscopies, and Empirical Correlations, Structural Chemistry, 14(2), 159- 174.
• [27] Kalaycı, T., Kaya Kınaytürk, N., Tunalı, B. 2022. Experimental and theoretical investigations (FTIR, UV-VIS spectroscopy, HOMO-LUMO, NLO and MEP analysis) of aminothiophenol isomers, Bulletin of the Chemical Society of Ethiopia, 35(3), 601-614.
• [28] Celik, S., Vagifli, F., Akyuz, S., Ozkok, F., Ozel, A. E., Dosler, S., Onul, N. 2022. Synthesis, vibrational spectroscopic investigation,molecular docking, antibacterial and antimicrobial studies of a new anthraquinone derivative compound, Spectroscopy Letters, 55(4), 259-277.
• [29] Rocha, M., Di Santo, A., Marcelo Arias, J., Gil D. M., Altabef, A. B. 2015. Ab-initio and DFT calculations on molecular structure, NBO, HOMO–LUMO study and a new vibrational analysis of 4-(Dimethylamino) Benzaldehyde, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 136, 635-643.
• [30] Demircioğlu, Z. 2022. 7-hidroksi-8-[4-metilpiperazin-1-yl)metil]2H-kromen-2-on Molekülünün Kimyasal Aktivite ve Moleküler Kenetlenme Çalışmaları, El-Cezerî Journal of Science and Engineering, 9(2), 598-606.
• [31] Guedes, I., Magalhaes, C., Dardenne, L. 2014. Receptor–ligand molecular docking, Biophysical Reviews , 6(1), 75-87.
• [32] Shi, J.H., Lou, Y.Y., Zhou, K.L., Pan, D.Q. 2018 Exploration of intermolecular interaction of calf thymus DNA with sulfosulfuron using multispectroscopic and molecular docking techniques, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 204, 209-216.
• [33] Sirajuddin, M., Ali, S., Badshah, A. 2013. Drug– DNA interactions and their study by UV–Visible, fluorescence spectroscopies and cyclic voltametry, Journal of Photochemistry and Photobiology B: Biology, 124, 1-19.
• [34] Zhang, Y., Wang, X., Ding, L. 2010. Interaction between tryptophan-vanillin Schiff base and herring sperm DNA, Journal of the Serbian Chemical Society, 75(9), 1191-1201.
• [35] Alleva, R., Manzella, N., Gaetani, S., Bacchetti, T. Bracci, M., Ciarapica, V., Monaco, F., Borghi, B. Amati, M., Ferretti, G., Tomasetti, M. 2018. Mechanism underlying the effect of long-term exposure to low dose of pesticides on DNA integrity, Environmental Toxicology, 33(4), 476-487.
• [36] Zhang, Y. , Zhang, G., Li, Y., Hu, Y. 2013. Probing the Binding of Insecticide Permethrin to Calf Thymus DNA by Spectroscopic Techniques Merging with Chemometrics Method, Agricultural and Food Chemistry, 61. 2638- 2647.
• [37] Aysan, Ö., Dede, B. 2020. Bazı Oksim Bileşiklerinin Bağlanma Özelliklerinin Moleküler Kenetlenme Yöntemiyle İncelenmesi, Journal of Natural and Applied Sciences, 24(2), 333-339.
• [38] Çelik, S., Ozkok, F., Ozel, A., Sahin, Y. M., Akyuz, S., Diren Sigirci, B., Basaran Kahraman, B., Darici, H., Karaoz, E. 2020. Synthesis, FT-IR and NMR characterization, antimicrobial activity, cytotoxicity and DNA docking analysis of a new anthraquinone derivate compound, Journal Of Bıomolecular Structure And Dynamıcs, 38(3), 756-770.
• [39] Ali, I., Lone, M. N., Al-Othman, Z., Al-Warthan, A. 2017. Insights into the Pharmacology of New Heterocycles Embedded with Oxopyrrolidine Rings: DNA Binding, Molecular Docking, and Anticancer Studies, Journal of Molecular Liquids, 234, 391-402.
• [40] Karami, K., Jamshidian, N., Zakariazadeh, M. 2019. Synthesis, characterization and molecular docking of new C,N-palladacycles containing pyridinium-derived ligands: DNA and BSA interaction studies and evaluation as anti-tumor agents, Applied Organometallic Chemistry, 33(3), e4728, 2019