SavedAdd your journal

Journals / ADYUTAYAM Dergisi / 2025 / Cilt: 13 Sayı: 2

DETERMINATION OF POTENTIAL BIOTECHNOLOGICAL TARGETS OF BRILLIANT BLUE BY USING COMBINATION OF IN SILICO TARGET FISHING AND MOLECULAR DOCKING TECHNIQUES

SİLİCO HEDEF BALIKÇILIĞI VE MOLEKÜLER YERLEŞTİRME TEKNİKLERİNİ BİRLİKTE KULLANARAK PARLAK MAVİ'NİN POTANSİYEL BİYOTEKNOLOJİK HEDEFLERİNİN BELİRLENMESİ

Mehmet Karadayı(ATATÜRK ÜNİVERSİTESİ)0000-0002-2473-0409
Selin Doğan(Atatürk Üniversitesi)0000-0003-0499-2169
Taha Yasin Koç(ATATÜRK ÜNİVERSİTESİ)0000-0002-7786-5462
Yusuf Gülşahin(ATATÜRK ÜNİVERSİTESİ)0000-0002-3770-2116
Medine Güllüce(ATATÜRK ÜNİVERSİTESİ)0000-0002-5957-8259
Pages
45–59
Publication Date
2025-12-29
DOI
—
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Thus, a valuable information on the potential targets of brilliant blue was gained for the biotechnology research.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Brillant blue (C47H49N3O7S2), also known as benzenemethanaminium or E133, is one of the most industrially used food colorant.
📊
Key Findings & Data:For this, 3D molecular structure of brilliant blue was obtained from PubChem Database (CID: 136664753).
💡
Conclusion & Impact:Thus, a valuable information on the potential targets of brilliant blue was gained for the biotechnology research.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:E133 · Gıda renklendirici · Hedef balıkçılığı

Abstract

Brillant blue (C47H49N3O7S2), also known as benzenemethanaminium or E133, is one of the most industrially used food colorant. Although use of brilliant blue is commonly accepted as safe in the food regulations, there is a growing concern in the nutrition and health experts due to its synthetic nature and presence of active groups in its molecular structure. In this regard, the present study conducted to investigate potential human targets of brilliant blue by using recent in silico tools. For this, 3D molecular structure of brilliant blue was obtained from PubChem Database (CID: 136664753). Target fishing studies was performed by using TargetNet, an open web server predicting the binding of multiple targets for the given molecules. Then, the results were further analyzed by molecular docking studies using Schrödinger Maestro Suite (ver. 13.9). According to the target fishing studies, 16 potential human targets including 5-hydroxytryptamine_receptor_1E, Bcl-2-related_protein_A1, Caspase-9, COUP_transcription_factor_2, Cytochrome_P450_2C9, DNA_(cytosine-5)-methyltransferase_1, DNA_dCdU-editing_enzyme_APOBEC-3A, Dual_specificity_protein_phosphatase_3, Galanin_receptor_type_3, G-protein_coupled_receptor_35, Hepatocyte_nuclear_factor_4-alpha, Nuclear_receptor_ROR-alpha, Perilipin-1, Perilipin-5, Toll-like_receptor_9, Tyrosine-protein_kinase_Fyn were determined. Molecular docking results revealed and validated the interactions, binding affinities between brilliant blue and the targets varied from -4.447 to -7.604 kcal/mol. Thus, a valuable information on the potential targets of brilliant blue was gained for the biotechnology research.

Özet

Brilliant blue (C47H49N3O7S2), benzenemethanaminium veya E133 olarak da bilinen, endüstriyel alanda en yaygın kullanılan gıda renklendiricilerinden biridir. Gıda mevzuatlarında brilliant blue kullanımı genel olarak güvenli kabul edilse de, sentetik yapısı ve moleküler yapısındaki aktif grupların varlığı nedeniyle beslenme ve sağlık uzmanları arasında artan bir endişe bulunmaktadır. Bu bağlamda, bu çalışma brilliant blue’nun potansiyel insan hedeflerini güncel in silico (bilgisayar destekli) araçlar kullanarak araştırmak amacıyla yürütülmüştür. Bu amaçla, brilliant blue’nun 3B moleküler yapısı PubChem Veritabanı’ndan (CID: 136664753) elde edilmiştir. Hedef belirleme çalışmaları, verilen molekül için birden fazla hedefle etkileşimi öngören açık erişimli bir web sunucusu olan TargetNet kullanılarak gerçekleştirilmiştir. Ardından, elde edilen sonuçlar Schrödinger Maestro Suite (sürüm 13.9) kullanılarak moleküler yerleştirme (docking) çalışmalarıyla analiz edilmiştir. Hedef avcılığı çalışmalarına göre -hydroxytryptamine_receptor_1E, Bcl-2-related_protein_A1, Caspase-9, COUP_transcription_factor_2, Cytochrome_P450_2C9, DNA_(cytosine-5)-methyltransferase_1, DNA_dCdU-editing_enzyme_APOBEC-3A, Dual_specificity_protein_phosphatase_3, Galanin_receptor_type_3, G-protein_coupled_receptor_35, Hepatocyte_nuclear_factor_4-alpha, Nuclear_receptor_ROR-alpha, Perilipin-1, Perilipin-5, Toll-like_receptor_9, Tyrosine-protein_kinase_Fyn olmak üzere 16 potansiyel insan hedefi belirlendi. Moleküler yerleştirme sonuçları, brilliant blue ile bu hedefler arasındaki etkileşimleri ve bağlanma afinitelerini ortaya koymuş olup, bağlanma enerjilerinin -4.447 ile -7.604 kcal/mol arasında değiştiği belirlenmiştir. Böylece, brilliant blue’nun potansiyel insan hedefleri hakkında biyoteknoloji araştırmaları açısından değerli bilgiler elde edilmiştir.

🔖

Cite This Article

Karadayı, M., Doğan, S., Koç, T. Y., Gülşahin, Y., Güllüce, M. (2025). DETERMINATION OF POTENTIAL BIOTECHNOLOGICAL TARGETS OF BRILLIANT BLUE BY USING COMBINATION OF IN SILICO TARGET FISHING AND MOLECULAR DOCKING TECHNIQUES. ADYUTAYAM Dergisi, Cilt: 13 Sayı: 2, 45–59. https://ajindex.com/articles/1441023

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (52)

  1. Ahmed, M. A., Al-Khalifa, A. S., Al-Nouri, D. M., & El-Din, M. F. S. (2021). Dietary intake of artificial food color additives containing food products by school-going children. Saudi Journal of Biological Sciences, 28(1), 27-34. https://doi.org/10.1016/j.sjbs.2020.08.025
  2. Allen, D. G., Allen, D., Waters, M. D., & Waters, M. D. (Eds.). (2013). Reducing, refining and replacing the use of animals in toxicity testing (Vol. 19, ss. 119-162). Royal Society of Chemistry. https://doi.org/10.1039/9781849737920
  3. Amchova, P., Kotolova, H., & Ruda-Kucerova, J. (2015). Health safety issues of synthetic food colorants. Regulatory Toxicology and Pharmacology, 73(3), 914-922. https://doi.org/10.1016/j.yrtph.2015.09.026
  4. Andersen, M. E., & Krewski, D. (2009). Toxicity testing in the 21st century: bringing the vision to life. Toxicological Sciences, 107(2), 324-330. https://doi.org/10.1093/toxsci/kfn255
  5. Bateman, B., Warner, J. O., Hutchinson, E., Dean, T., Rowlandson, P., Gant, C., & Grundy, J. (2004). The effects of a double-blind, placebo-controlled, artificial food coloring challenge on hyperactivity in children. The Lancet, 364(9433), 1565–1571. https://doi.org/10.1016/S0140-6736(04)17201-7
  6. Berman, H. M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T. N., Weissig, H., Ilya, N. S., & Bourne, P. E. (2000). The protein data bank. Nucleic Acids Research, 28(1), 235-242. https://doi.org/10.1093/nar/28.1.235
  7. Bužga, M., Machytka, E., Dvořáčková, E., Švagera, Z., Stejskal, D., Máca, J., & Král, J. (2022). Methylene blue: a controversial diagnostic acid and medication? Toxicology Research, 11(5), 711-717. https://doi.org/10.1093/toxres/tfac050
  8. Chen, L., & Yu, J. (2016). Modulation of Toll-like receptor signaling in innate immunity by natural products. International Immunopharmacology, 37, 65-70. https://doi.org/10.1016/j.intimp.2016.02.005
  9. Chen, Y. H., Tseng, C. P., How, S. C., Lo, C. H., Chou, W. L., & Wang, S. S. S. (2016). Amyloid fibrillogenesis of lysozyme is suppressed by a food additive Brilliant Blue FCF. Colloids and Surfaces B: Biointerfaces, 142, 351-359. https://doi.org/10.1016/j.colsurfb.2016.02.064
  10. Cornélie, S., Hoebeke, J., Schacht, A. M., Bertin, B., Vicogne, J., Capron, M., & Riveau, G. (2004). Direct evidence that toll-like receptor 9 (TLR9) functionally binds plasmid DNA by specific cytosine-phosphate-guanine motif recognition. Journal of Biological Chemistry, 279(15), 15124-15129. https://doi.org/10.1074/jbc.M313406200
  11. Curry, T., Epstein, T., Smith, R., & Kopelman, R. (2013). Photothermal therapy of cancer cells mediated by blue hydrogel nanoparticles. Nanomedicine, 8(10), 1577-1586. https://doi.org/10.2217/nnm.12.190
  12. de Lima Barizão, A. C., Silva, M. F., Andrade, M., Brito, F. C., Gomes, R. G., & Bergamasco, R. (2020). Green synthesis of iron oxide nanoparticles for tartrazine and bordeaux red dye removal. Journal of Environmental Chemical Engineering, 8(1), 103618. https://doi.org/10.1016/j.jece.2019.103618
  13. Erdoğan, M., Taslimi, P., & Tuzun, B. (2021). Synthesis and docking calculations of tetrafluoronaphthalene derivatives and their inhibition profiles against some metabolic enzymes. Archiv der Pharmazie, 354(6), 2000409. https://doi.org/10.1002/ardp.202000409
  14. Ferreira, L. G. B., Faria, R. X., Ferreira, N. C. D. S., & Soares-Bezerra, R. J. (2016). Brilliant Blue Dyes in daily food: How could purinergic system be affected? International Journal of Food Science, 2016(1), 7548498. https://doi.org/10.1155/2016/7548498
  15. Fiorito, S., Epifano, F., Palumbo, L., Collevecchio, C., Spogli, R., & Genovese, S. (2023). Separation and quantification of Tartrazine (E102) and Brilliant Blue FCF (E133) in green colored foods and beverages. Food Research International, 172, 113094. https://doi.org/10.1016/j.foodres.2023.113094
  16. Ford, K. A. (2017). Refinement, reduction, and replacement of animal toxicity tests by computational methods. ILAR Journal, 57(2), 226-233. https://doi.org/10.1093/ilar/ilw031
  17. Galati, S., Di Stefano, M., Martinelli, E., Poli, G., & Tuccinardi, T. (2021). Recent advances in in silico target fishing. Molecules, 26(17), 5124. https://doi.org/10.3390/molecules26175124
  18. Ganesh, P. S., Kim, S. Y., Kaya, S., Salim, R., Shimoga, G., & Lee, S. H. (2021). Quantum chemical studies and electrochemical investigations of polymerized Brilliant Blue-modified carbon paste electrode for in vitro sensing of pharmaceutical samples. Chemosensors, 9(6), 135. https://doi.org/10.3390/chemosensors9060135
  19. Ghorpade, V. M., Deshpande, S. S., & Salunkhe, D. K. (1995). Food colors (Vol. 4). Marcel Dekker Inc. New York.
  20. Gičević, A., Hindija, L., & Karačić, A. (2020). Toxicity of azo dyes in pharmaceutical industry. In CMBEBIH 2019: Proceedings of the International Conference on Medical and Biological Engineering, 16 ̶̶ 18 May 2019, Banja Luka, Bosnia and Herzegovina (ss. 581-587). Springer International Publishing. https://doi.org/10.1007/978-3-030-17971-7
  21. Gómez, A., Alarcón, A., Acosta, W., & Malagón, A. (2024). Silico hedef balıkçılığı kullanılarak glifosatın potansiyel insan hedeflerinin belirlenmesi. Hesaplamalı Toksikoloji, 30, 100306. https://doi.org/10.1016/j.comtox.2024.100306 Gonzalez, F. J. (2008). Regulation of hepatocyte nuclear factor 4 \alpha -mediated transcription. Drug Metabolism and Pharmacokinetics, 23(1), 2-7. https://doi.org/10.2133/dmpk.23.2
  22. Guo, J., Wu, H., Du, L., & Fu, Y. (2013). Determination of Brilliant Blue FCF in food and cosmetic samples by ionic liquid independent disperse liquid–liquid micro-extraction. Analytical Methods, 5(16), 4021-4026. https://doi.org/10.1039/c3ay40362a
  23. Jasińska, A., Paraszkiewicz, K., Słaba, M., & Długoński, J. (2015). Microbial decolorization of triphenylmethane dyes. In Microbial degradation of synthetic dyes in wastewaters (ss. 169-186). https://doi.org/10.1007/978-3-319-10942-8
  24. Kale, J., Osterlund, E. J., & Andrews, D. W. (2018). BCL-2 family proteins: changing partners in the dance towards death. Cell Death & Differentiation, 25(1), 65-80. https://doi.org/10.1038/cdd.2017.186
  25. Kallen, J., & Schlaeppi, J. M. (2014). Structure and function of \text{ROR} nuclear receptors. Current Topics in Medicinal Chemistry, 14(12), 1304–1315. https://doi.org/10.2174/1568004114666140825123019 Kamerlin, N., Delcey, M. G., Manzetti, S., & Van der Spoel, D. (2020). Toward a computational ecotoxicity assay. Journal of Chemical Information and Modeling, 60(8), 3792-3803. https://doi.org/10.1021/acs.jcim.0c00574
  26. Kavlock, R. J., Ankley, G., Blancato, J., Breen, M., Conolly, R., Dix, D., Houch, K., Hubal, E., Judson, R., Rabinowitz, J., Richard, A., Setzer, R. W., Sah, I., Villeneuve, D., & Weber, E. (2008). Computational toxicology-a state of the science mini review. Toxicological Sciences, 103(1), 14-27. https://doi.org/10.1093/toxsci/kfm297 Koç, K., & Pandir, D. (2018). All aspect of toxic effect of Brilliant Blue and sunset yellow in Allium cepa roots. Cytotechnology, 70, 449-463. https://doi.org/10.1007/s10616-017-0161-9
  27. Lanfumey, L., & Hamon, M. (2004). 5-HT1 receptors. Current Drug Targets-CNS & Neurological Disorders, 3(1), 1-10. https://doi.org/10.2174/1568007043482570
  28. Le, J., Xiao, X., Zhang, D., Feng, Y., Wu, Z., Mao, Y., Mou, Ç., Xie, Y., Çen, X., Liu, H., & Cui, W. (2022). Neuroprotective Effects of an Edible Pigment Brilliant Blue FCF against Behavioral Abnormity in MCAO Rats. Pharmaceuticals, 15(8), 1018. https://doi.org/10.3390/ph15081018
  29. Legler, J. (2010). Epigenetics: an emerging field in environmental toxicology. Integrated Environmental Assessment & Management, 6(2). https://doi.org/10.1002/ieam.40
  30. Li, R., Shang, Y., Hu, X., Yu, Y., Zhou, T., Xiong, W., & Zou, X. (2020). ATP/P2X7r axis mediates the pathological process of allergic asthma by inducing M2 polarization of alveolar macrophages. Experimental Cell Research, 386(1), 111708. https://doi.org/10.1016/j.yexcr.2019.111708
  31. Madhavi Sastry, G., Adzhigirey, M., Day, T., Annabhimoju, R., & Sherman, W. (2013). Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. Journal of Computer-Aided Molecular Design, 27, 221-234. https://doi.org/10.1007/s10822-013-9644-8
  32. Martins, N., Roriz, C. L., Morales, P., Barros, L., & Ferreira, I. C. (2017). Coloring attributes of betalains: a key emphasis on stability and future applications. Food & Function, 8(4), 1357-1372. https://doi.org/10.1039/C7FO00144D
  33. Matsufujı, H., Kusaka, T., Tsukuda, M., Chıno, M., Kato, Y., Nakamura, M., Goda, Y., Toyoda M., & Takeda, M. (1998). Structural determination of subsidiary colors in commercial Food Blue No. 1 (Brilliant Blue FCF) product. Food Hygiene and Safety Science, 39(1), 7-12_1. https://doi.org/10.3358/shokueishi.39.7
  34. Ozturk, O., Kahveci, S., Oflamaz, A. O., Ucar, S., Yilmaz, S., & Doganyigit, Z. (2023). Effect of Tartrazine on Rat Placenta. Bozok Medical Journal, 13(4), 123-130. https://doi.org/10.16919/bozoktip.1366830
  35. Raies, A. B., & Bajic, V. B. (2016). In silico toxicology: computational methods for the prediction of chemical toxicity. Wiley Interdisciplinary Reviews: Computational Molecular Science, 6(2), 147-172. https://doi.org/10.1002/wcms.1240
  36. Renita, A. A., Gajaria, T. K., Sathish, S., Kumar, J. A., Lakshmi, D. S., Kujawa, J., & Kujawski, W. (2023). Progress and prospective of the industrial development and applications of \text{ECO} -friendly colorants: an insight into environmental impact and Sustainability issues. Foods, 12(7), 1521. https://doi.org/10.3390/foods12071521
  37. Rovina, K., Siddiquee, S., & Shaarani, S. M. (2017). A review of extraction and analytical methods for the determination of tartrazine (E 102) in foodstuffs. Critical Reviews in Analytical Chemistry, 47(4), 309-324. https://doi.org/10.1080/10408347.2017.1287558
  38. Saleh, M. M., Hashem, E. Y., & Al-Salahi, N. O. (2016). Oxidation and complexation-based spectrophotometric methods for sensitive determination of tartrazine \text{E102} in some commercial food samples. Computational Chemistry, 4(02), 51. https://doi.org/10.4236/cc.2016.42005
  39. Sandholm, J., & Selander, K. S. (2014). Toll-like receptor 9 in breast cancer. Frontiers in Immunology, 5, 330. https://doi.org/10.3389/fimmu.2014.00330
  40. Saxena, B., & Sharma, S. (2015). Food color induced hepatotoxicity in Swiss albino rats, Rattus norvegicus. Toxicology International, 22(1), 152. https://doi.org/10.4103/0971-6580.172286
  41. Shelley, J. C., Cholleti, A., Frye, L. L., Greenwood, J. R., Timlin, M. R., & Uchimaya, M. (2007). Epik: a software program for pK prediction and protonation state generation for drug-like molecules. Journal of Computer-Aided Molecular Design, 21, 681-691. https://doi.org/10.1007/s10822-007-9133-z
  42. Silva, M. M., Reboredo, F. H., & Lidon, F. C. (2022). Food colour additives: A synoptical overview on their chemical properties, applications in food products, and health side effects. Foods, 11(3), 379. https://doi.org/10.3390/foods11030379
  43. Stevens, A. J., Rucklidge, J. J., & Kennedy, M. A. (2018). Epigenetics, nutrition and mental health. Is there a relationship? Nutritional Neuroscience, 21(9), 602-613. https://doi.org/10.1080/1028415X.2017.1331524
  44. Takeda, M. (1998). Structural determination of subsidiary colors in commercial Food Blue No. 1 (Brilliant Blue FCF) product. Food Hygiene and Safety Science (Shokuhin Eiseigaku Zasshi), 39(1), 7-12_1. https://doi.org/10.3358/shokueishi.39.7
  45. Tanaka, T., Takahashi, O., Oishi, S., & Ogata, A. (2008). Effects of tartrazine on exploratory behavior in a three-generation toxicity study in mice. Reproductive Toxicology, 26(2), 156-163. https://doi.org/10.1016/j.reprotox.2008.07.001
  46. Tao, X., Huang, Y., Wang, C., Chen, F., Yang, L., Ling, L., Zhenming, C., & Chen, X. (2020). Recent developments in molecular docking technology applied in food science: a review. International Journal of Food Science & Technology, 55(1), 33-45. https://doi.org/10.1111/ijfs.14325
  47. Tortosa, V., Pietropaolo, V., Brandi, V., Macari, G., Pasquadibisceglie, A., & Polticelli, F. (2020). Computational methods for the identification of molecular targets of toxic food additives. Butylated hydroxytoluene as a case study. Molecules, 25(9), 2229. https://doi.org/10.3390/molecules25092229 Vollmer, J. (2006). TLR9 in health and disease. International Reviews of Immunology, 25(3-4), 155-181. https://doi.org/10.1080/08830180600743107
  48. Wang, C., Yuan, W., Hu, A., Zhang, Y., Chen, J., Li, X., & Zhang, L. (2020). Paraventricular nucleus P2X7 receptors aggravate acute myocardial infarction injury via ROS-induced vasopressin-V1b activation in rats. Journal of Molecular and Cellular Cardiology, 145, 94–105. https://doi.org/10.1016/j.yjmcc.2020.05.005
  49. Wang, L., & Xie, X. Q. (2014). Computational target fishing: what should chemogenomics researchers expect for the future of in silico drug design and discovery? Future Medicinal Chemistry, 6(3), 247-249. https://doi.org/10.4155/fmc.14.5
  50. Wang, Y. C., Cui, Y., Cui, J. Z., Sun, L. Q., Cui, C. M., Zhang, H. A., Zhu, H. X., Li, R., Tian, Y. X, & Gao, J. L. (2015). Neuroprotective effects of Brilliant Blue G on the brain following traumatic brain injury in rats. Molecular Medicine Reports, 12(2), 2149-2154. https://doi.org/10.3892/mmr.2015.3607
  51. Weimann, S., Skudlik, C., & John, S. M. (2010). Allergic contact dermatitis caused by the blue pigment VINAMON Blue BX FW - a Phthalocyanine Blue in a vinyl glove. JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 8(10), 820-822. https://doi.org/10.1111/j.1610-0387.2010.07355.x
  52. Wu, S., Yin, Z. Z., Chen, X., Wang, X., Wu, D., & Kong, Y. (2020). Electropolymerized melamine for simultaneous determination of nitrite and tartrazine. Food Chemistry, 333, 127532. https://doi.org/10.1016/j.foodchem.2020.127532