A Structure-based Design Approach to Catharanthus roseus Phytoconstituents as Potential Inhibitors of B-Cell Lymphoma 6 Protein

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Year : June 30, 2023 | Volume : 01 | Issue : 02 | Page : 41-34

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Shahid Attar, Samiksha Bhor

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    1. Student, Bioinformatics Associate,Department of Bioinformatics, BioNome, Department of Biotechnology, BioNome,Karnataka, Karnataka,India, India

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    Abstract

    n Objectives: Lymphoma is a cancerous disease. It develops into millions of people worldwide. Identify the naturally active compounds from Catharanthus roseus, they have multiple values in the medicinal field of Siddha, and Indian Ayurveda are used as a disease-preventing agent. Drug illness prediction, toxicity prediction, statistical information, molecular docking, as well as absorption, distribution, metabolism, and excretion (ADME) analysis are used to predict the fit ligand as a drug. Methods: The database of protein data bank (PDB) was used to retrieve the BCL6 protein and its chains after the purification. The poor binding affinity of ligands with target protein was removed, ADMET analysis and Swiss-ADME lab webserver were used for drug-likeness analysis, and molecular docking is done with the PyRx. Results: The dihedral angles Φ and ψ combination in the backbone of protein is shown in the Ramachandran plot analysis. The five compounds of C. roseus have a potential binding affinity with BCL6 found in molecular docking. ADMET profile and docking interaction showed five compounds Perivine, Alstonine, Quercetin, 16-Methoxytabersonine, and Vindolininol are possess the properties of the drug and safe to use. Conclusion: The previous and present studies suggest that Perivine, Alstonine, Quercetin, 16-Methoxytabersonine, and Vindolininol could inhibit the chain A, B, and C of BCL6 protein and have significant affinity binding. The therapeutic strategies against B-cell lymphoma interpreted based on molecular binding and interactionn

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    Keywords: Catharanthus roseus, B-cell lymphoma, Cancer, Phytocompound, BCL6, Auto-docking, ADMET analysis.

    n [if 424 equals=”Regular Issue”][This article belongs to International Journal of Bioinformatics and Computational Biology(ijbcb)]n

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    [/if 424][if 424 equals=”Special Issue”][This article belongs to Special Issue under section in International Journal of Bioinformatics and Computational Biology(ijbcb)][/if 424][if 424 equals=”Conference”]This article belongs to Conference [/if 424]

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    How to cite this article:n Shahid Attar, Samiksha Bhor A Structure-based Design Approach to Catharanthus roseus Phytoconstituents as Potential Inhibitors of B-Cell Lymphoma 6 Protein ijbcb June 30, 2023; 01:41-34

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    How to cite this URL: Shahid Attar, Samiksha Bhor A Structure-based Design Approach to Catharanthus roseus Phytoconstituents as Potential Inhibitors of B-Cell Lymphoma 6 Protein ijbcb June 30, 2023n {cited June 30, 2023};01:41-34. Available from: https://journals.stmjournals.com/ijbcb/article=June 30, 2023/view=0/

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    1. Mugnaini, E. N., & Ghosh, N. (2016). Lymphoma. Primary Care: Clinics in Office Practice, 43(4), 661–675. DOI: 10.1016/j.pop.2016.07.012
    2. Leeman-Neill, R. J., & Bhagat, G. (2018). BCL6 as a therapeutic target for lymphoma. Expert Opinion on Therapeutic Targets, 22(2), 143 152. DOI: 10.1080/14728222.2018.1420782
    3. Martelli, A., Evangelisti, C., Y. Follo, M., Ramazzotti, G., Fini, M., Giardino, R., … Cocco, L. (2011). Targeting the Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Signaling Network in Cancer Stem Cells. Current Medicinal Chemistry, 18(18), 2715–2726. DOI: 10.2174/092986711796011201
    4. Chen, L., Monti, S., Juszczynski, P., Ouyang, J., Chapuy, B., Neuberg, D., … Shipp, M. A. (2013). SYK Inhibition Modulates Distinct PI3K/AKT- Dependent Survival Pathways and Cholesterol Biosynthesis in Diffuse Large B Cell Lymphomas. Cancer Cell, 23(6), 826–838. DOI: 10.1016/j.ccr.2013.05.002
    5. Isakov, N. (2018). Protein kinase C (PKC) isoforms in cancer, tumor promotion and tumor suppression. Seminars in Cancer Biology, 48, 36–52. DOI: 10.1016/j.semcancer.2017.04.012
    6. Agarwal, N. K., Qu, C., Kunkulla, K., Liu, Y., & Vega, F. (2013). Transcriptional Regulation of Serine/Threonine Protein Kinase (AKT) Genes by Glioma-associated Oncogene Homolog 1. Journal of Biological Chemistry, 288(21), 15390–15401. DOI: 10.1074/jbc.m112.425249
    7. Xiu, Y., Dong, Q., Fu, L., Bossler, A., Tang, X., Boyce, B., … Zhao, C. (2020). Coactivation of NF-κB and Notch signaling is sufficient to induce B-cell transformation and enables B-myeloid conversion. Blood, 135(2), 108–120. DOI: 10.1182/blood.2019001438
    8. Knight, T., & Irving, J. A. E. (2014). Ras/Raf/MEK/ERK Pathway Activation in Childhood Acute Lymphoblastic Leukemia and Its Therapeutic Targeting. Frontiers in Oncology, 4. DOI:3389/fonc.2014.00160
    9. Abuelgasim, K. A., Shammari, R. A., Alshieban, S., Alahmari, B., Alzahrani, M., Alhejazi, A., … Damlaj, M. (2021). Impact of cluster of differentiation 20 expression and rituximab therapy in classical Hodgkin lymphoma: Real world experience. Leukemia Research Reports, 15, 100240. DOI: 10.1016/j.lrr.2021.100240
    10. William, Basem & Bongu, Navneeth & Bast, Martin & Bociek, Robert & Bierman, Philip & Vose, Julie & Armitage, James. (2013). The utility of lactate dehydrogenase in the follow up of patients with diffuse large B-cell lymphoma. Revista brasileira de hematologia e hemoterapia. 35. 189-91. DOI: 10.5581/1516-8484.20130055
    11. Read, K. A., Powell, M. D., Baker, C. E., Sreekumar, B. K., Ringel-Scaia, V. M., Bachus, H., … Oestreich, K. J. (2017). Integrated STAT3 and Ikaros Zinc Finger Transcription Factor Activities Regulate Bcl-6 Expression in CD4+Th Cells. The Journal of Immunology, 199(7), 2377–2387. DOI: 10.4049/jimmunol.1700106
    12. Mirlekar B, Wang Y, Li S, Zhou M, Entwistle S, De Buysscher T, Morrison A, Herrera G, Harris C, Vincent BG, Ting JP, Rashid N, Kim WY, Yeh JJ, Pylayeva-Gupta Y. (2022) Balance between immunoregulatory B cells and plasma cells drives pancreatic tumor immunity. Cell Rep Med. 2022 Sep 20;3(9):100744. DOI: 10.1016/j.xcrm.2022.100744.
    13. Lien, C., Fang, C.-M., Huso, D., Livak, F., Lu, R., & Pitha, P. M. (2010). Critical role of IRF-5 in regulation of B-cell differentiation. Proceedings of the National Academy of Sciences, 107(10), 4664–4668. DOI: 10.1073/pnas.0911193107
    14. Zhao, S., Shen, W., Yu, J., & Wang, L. (2018). TBX21 predicts prognosis of patients and drives cancer stem cell maintenance via the TBX21–IL-4 pathway in lung adenocarcinoma. Stem Cell Research & Therapy, 9(1). DOI: 10.1186/s13287-018-0820-6
    15. Chevrier, S., Kratina, T., Emslie, D., Tarlinton, D. M., & Corcoran, L. M. (2017). IL4 and IL21 cooperate to induce the high Bcl6 protein level required for germinal center formation. Immunology and Cell Biology, 95(10), 925–932. DOI: 10.1038/icb.2017.71
    16. Wang, H.-Y., & Zu, Y. (2017). Diagnostic Algorithm of Common Mature B-Cell Lymphomas by Immunohistochemistry. Archives of Pathology & Laboratory Medicine, 141(9), 1236–1246. DOI: 10.5858/arpa.2016-0521-ra
    17. Pillai, R. K., Sathanoori, M., Van Oss, S. B., & Swerdlow, S. H. (2013). Double-hit B-cell Lymphomas With BCL6 and MYC Translocations Are Aggressive, Frequently Extranodal Lymphomas Distinct From BCL2 Double-hit B-cell Lymphomas. The American Journal of Surgical Pathology, 37(3), 323–332. DOI: 10.1097/pas.0b013e31826cebad
    18. Jaye, D., Iqbal, J., Fujita, N., Geigerman, C., Li, S., Karanam, S., … Wade, P. (2007). The BCL6-associated transcriptional co-repressor, MTA3, is selectively expressed by germinal centre B cells and lymphomas of putative germinal centre derivation. The Journal of Pathology, 213(1), 106–115. DOI: 10.1002/path.2199
    19. McLachlan, T., Matthews, W. C., Jackson, E. R., Staudt, D. E., Douglas, A. M., Findlay, I. J., Persson, M. L., Duchatel, R. J., Mannan, A., Germon, Z. P., & Dun, M. D. (2022). B-cell Lymphoma 6 (BCL6): From Master Regulator of Humoral Immunity to Oncogenic Driver in Pediatric Cancers. In Molecular cancer research : MCR (Vol. 20, Issue 12, pp. 1711–1723). NLM (Medline). DOI:1158/1541-7786.MCR-22-0567
    20. Cortiguera, M. G., García-Gaipo, L., Wagner, S. D., León, J., Batlle-López, A., & Delgado, M. D. (2019). Suppression of BCL6 function by HDAC inhibitor mediated acetylation and chromatin modification enhances BET inhibitor effects in B-cell lymphoma cells. Scientific Reports, 9(1). DOI: 10.1038/s41598-019-52714-4
    21. Das A, Sarkar S, Bhattacharyya S, Gantait S. (2020) Biotechnological advancements in Catharanthus roseus (L.) G. Don. Appl Microbiol Biotechnol. 2020 Jun;104(11):4811-4835. DOI: 10.1007/s00253-020-10592-1.
    22. Bitencourt-Ferreira, G., Pintro, V. O., & de Azevedo, W. F. (2019). Docking with AutoDock4. Docking Screens for Drug Discovery, 125–148. DOI: 10.1007/978-1-4939-9752-7_9
    23. Ahmad, K. F., Melnick, A., Lax, S., Bouchard, D., Liu, J., Kiang, C.-L., … Privé, G. G. (2003). Mechanism of SMRT Corepressor Recruitment by the BCL6 BTB Domain. Molecular Cell, 12(6), 1551–1564. DOI:10.1016/s1097-2765(03)00454-4
    24. Riyaphan J, Pham DC, Leong MK, Weng CF. (2021). In Silico Approaches to Identify Polyphenol Compounds as α-Glucosidase and α-Amylase Inhibitors against Type-II Diabetes. Biomolecules. 2021 Dec 14;11(12):1877. DOI: 10.3390/biom11121877.
    25. 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(3), 221–234. DOI: 10.1007/s10822-013-9644-8
    26. Kumar S, Singh B, Singh R. (2022). Catharanthus roseus (L.) G. Don: A review of its ethnobotany, phytochemistry, ethnopharmacology and toxicities. J Ethnopharmacol. 2022 Feb 10;284:114647. DOI: 10.1016/j.jep.2021.114647
    27. Long, K., Kostman, S. J., Fernandez, C., Burnett, J. C., & Huryn, D. M. (2019). Do Zebrafish Obey Lipinski Rules? ACS Medicinal Chemistry Letters, 10(6), 1002–1006. DOI: 10.1021/acsmedchemlett.9b00063
    28. Shikov, A. N., Flisyuk, E. V., Obluchinskaya, E. D., & Pozharitskaya, O. N. (2020). Pharmacokinetics of Marine-Derived Drugs. Marine Drugs, 18(11), 557. doi:10.3390/md18110557
    29. Dallakyan, S., & Olson, A. J. (2014). Small-Molecule Library Screening by Docking with PyRx. Chemical Biology, 243–250. DOI: 10.1007/978-1-4939-2269-7_19
    30. Banerjee, P., Eckert, A. O., Schrey, A. K., & Preissner, R. (2018). ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Research, 46(W1), W257–W263. DOI: 10.1093/nar/gky318
    31. Jendele, L., Krivak, R., Skoda, P., Novotny, M., & Hoksza, D. (2019). PrankWeb: a web server for ligand binding site prediction and visualization. Nucleic Acids Research. DOI: 10.1093/nar/gkz424
    32. Tian, W., Chen, C., Lei, X., Zhao, J., & Liang, J. (2018). CASTp 3.0: computed atlas of surface topography of proteins. Nucleic Acids Research, 46(W1), W363–W367. DOI: 10.1093/nar/gky473
    33. Okeke, Ifeanyichukwu & Okeke, Cosmas. (2022). Molecular Docking and Analysis of In Silico Generated Ligands Against SARS-CoV-2 Spike and Replicase Proteins. 10.21203/rs.3.rs-2069911/v1.
    34. Rajashekara S, Reena D, Mainavi MV, Sandhya LS, Baro U. (2022). Biological isolation and characterization of Catharanthus roseus (L.) G. Don methanolic leaves extracts and their assessment for antimicrobial, cytotoxic, and apoptotic activities. BMC Complement Med Ther. 2022 Dec 9;22(1):328. DOI: 10.1186/s12906-022-03810-y
    35. Bhayana T, Gupta S. (2022). Elucidating the antifungal activity and mechanism of action of bioactive phytochemicals against fungal dermatitis isolates. Arch Dermatol Res. 2022 Nov 27. DOI: 10.1007/s00403-022-02475-4
    36. Patel, S. K., Khedkar, V. M., Jha, P. C., Jasrai, Y. T., Pandya, H. A., George, L.-B., … Skelton, A. A. (2015). Molecular interaction of selected phytochemicals under the charged environment ofPlasmodium falciparumchloroquine resistance transporter (PfCRT) model. Journal of Biomolecular Structure and Dynamics, 34(2), 290–303. DOI: 10.1080/07391102.2015.1028449
    37. Pham, H. N. T., Sakoff, J. A., Vuong, Q. V., Bowyer, M. C., & Scarlett, C. J. (2019). Phytochemical, antioxidant, anti-proliferative and antimicrobial properties of Catharanthus roseus root extract, saponin-enriched and aqueous fractions. Molecular Biology Reports, 46(3), 3265–3273. DOI: 10.1007/s11033-019-04786-8
    38. Pham, H. N. T., Sakoff, J. A., Vuong, Q. V., Bowyer, M. C., & Scarlett, C. J. (2018). Comparative cytotoxic activity between kaempferol and gallic acid against various cancer cell lines. Data in Brief, 21, 1033–1036. DOI: 10.1016/j.dib.2018.10.121
    39. Shanbhag, S., & Ambinder, R. F. (2017). Hodgkin lymphoma: A review and update on recent progress. CA: A Cancer Journal for Clinicians, 68(2), 116–132. DOI: 10.3322/caac.21438
    40. Okuni M, Yakushijin K, Sakai Y, Suto H, Ichikawa H, Sakai R, Kakiuchi S, Kurata K, Mizutani Y, Kitao A, Miyata Y, Saito Y, Kawamoto S, Yamamoto K, Ito M, Matsuoka H, Minami H. (2018). A Case of Classical Hodgkin Lymphoma with Total Lymph Node Infarction. J Clin Exp Hematop. 2018 Mar 16;58(1):24-26. DOI: 10.3960/jslrt.17026
    41. Davoodvandi, A., Shabani Varkani, M., Clark, C. C. T., & Jafarnejad, S. (2020). Quercetin as an anticancer agent: Focus on esophageal cancer. Journal of Food Biochemistry. DOI: 10.1111/jfbc.13374
    42. Hashemzaei, M., Far, A. D., Yari, A., Heravi, R. E., Tabrizian, K., Taghdisi, S. M., … Rezaee, R. (2017). Anticancer and apoptosis-inducing effects of quercetin in vitro and in vivo. Oncology Reports, 38(2), 819–828. DOI: 10.3892/or.2017.5766
    43. Qu, Y., Easson, M. L. A. E., Froese, J., Simionescu, R., Hudlicky, T., & De Luca, V. (2015). Completion of the seven-step pathway from tabersonine to the anticancer drug precursor vindoline and its assembly in yeast. Proceedings of the National Academy of Sciences, 112(19), 6224–6229. DOI: 10.1073/pnas.1501821112
    44. Kalaria, Rishee & Patel, Hiren. (2020). Naturally occurring phytochemical as inhibitors from Catharanthus roseus: An In-silico approaches for drug development against COVID-19. DOI: 10.21203/rs.3.rs-116443/v1
    45. Asgharian P, Tazehkand AP, Soofiyani SR, Hosseini K, Martorell M, Tarhriz V, Ahangari H, Cruz-Martins N, Sharifi-Rad J, Almarhoon ZM, Ydyrys A, Nurzhanyat A, Yessenbekova A, Cho WC. (2021) Quercetin Impact in Pancreatic Cancer: An Overview on Its Therapeutic Effects. Oxid Med Cell Longev. 2021 Nov 3;2021:4393266. DOI: 10.1155/2021/4393266

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    Volume 01
    Issue 02
    Received May 9, 2023
    Accepted May 31, 2023
    Published June 30, 2023

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