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The cytotoxicity of brazilin and derivatives might be due to an inhibition of the c-Src-kinase

Annemarie E Kramell, Bianka Siewert, Jana Wiese, Veronika Temml, Hans-Peter Deigner, Ahmed Al-Harrasi, René Csuk

Abstract


In this study, several derivatives of brazilin with different lipophilicity were synthesized. The cytotoxic potential of these substances was evaluated in S.R.B. assays. A triacetylated brazilin reaction with PBr3 or PCl3 and a subsequent aqueous workup led to the formation of a phosphorous ester containing two triacetylated brazilin subunits. This compound held unexpected high cytotoxicity. In this study, Brazilin-derived triacetate showed good cytotoxic activity (EC50 = 5.2 M) concerning A2780 carcinoma cells. The results from docking studies suggest that brazilin's cytotoxicity might be due to an inhibition of a tyrosine kinase in an ATP-competitive manner.


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- N.P. Nirmal, M.S. Rajput, R.G.S.V. Prasad, M. Ahmad, Brazilin from Caesalpinia sappan heartwood and its pharmacological activities: A review, Asian Pac. J. Trop. Med., 2015, 8, 421-430.

- R.W. Dapson, C.L. Bain, Brazilwood, sappanwood, brazilin and the red dye brazilein: from textile dyeing and folk medicine to biological staining and musical instruments, Biotech. Histochem., 2015, 90, 401-423.

- D. Cardon, Natural Dyes: Sources, Tradition, Technology and Science, Archetype Publications Ltd., London, 2007.

- J.H. Hofenk de Graaff, The Colourful Past: Origins, Chemistry and Identification of Natural Dyestuffs, Abegg-Stiftung and Archetype Publications Ltd., London, 2004.

- R. Pratt, Y. Yuzuriha, Antibacterial activity of the heartwood of Haematoxylon braziletto, J. Am. Pharm. Assoc., 1959, 48, 69-72.

- H.X. Xu, S.F. Lee, The antibacterial principle of Caesalpinia sappan, Phytother. Res., 2004, 18, 647-651.

- C.K. Moon, K.S. Park, S.G. Kim, H.S. Won, J.H. Chung, Brazilin protects cultured rat hepatocytes from bromochloroform-induced toxicity, Drug Chem. Toxicol., 1992, 15, 81-91.

- B.M. Choi, J.A. Lee, S.S. Gao, S.Y. Eun, Y.S. Kim, S.Y. Ryu, Y.H. Choi, R. Park, D.Y. Kwon, B.-R. Kim, brazilin and the extract from Caesalpinia sappan L. protect oxidative injury through the expression of heme oxygenase-1, BioFactors, 2007, 30, 149-157.

- B.M. Choi, B.R. Kim, Upregulation of heme oxygenase-1 by brazilin via the phosphatidylinositol 3-kinase/Akt and ERK pathways and its protective effect against oxidative injury, Eur. J. Pharmacol., 2008, 580, 12-18.

- Y. Sasaki, T. Hosokawa, M. Nagai, S. Nagumo, In vitro study for inhibition of NO production about constituents of Sappan lignum, Biol. Pharm. Bull., 2007, 30, 193-196.

- C.T. Yen, K. Nakagawa-Goto, T.L. Hwang, P.C. Wu, S.L. Morris-Natschke, W.C. Lai, K.F. Bastow, F.R. Chang, Y.C. Wu, K.H. Lee, Antitumor agents. 271: Total synthesis and evaluation of brazilein and analogs as anti-inflammatory and cytotoxic agents, Bioorg. Med. Chem. Lett., 2010, 20, 1037-1039.

- C. Zhang, J. Zhang, H. Rao, J. Yang, X. Wang, X. Peng, Investigation on the interaction of brazilin with bovine serum albumin using multi-spectroscopic and computational methods: Exploring vthe binding mechanism and inhibitory effect on amyloid aggregation, Microchem. J., 2020, 159, 105529.

- G. Henriquez, L. Mendez, A. Varela-Ramirez, E. Guerrero, M. Narayan, Neuroprotective effect of brazilin on amyloid b (25-35)-induced pathology in human neuroblastoma model, A.C.S. Omega, 2020, 5, 13785-13792.

- D.Y. Lee, M.K. Lee, G.S. Kim, H.J. Noh, M.H. Lee, Brazilin inhibits growth and induces apoptosis in human glioblastoma cells, Molecules, 2013, 18, 2449-2457.

- W.J. Du, J.J. Guo, M.T. Gao, S.Q. Hu, X.Y. Dong, Y.F. Han, F.F. Liu, S. Jiang, Y. Sun, Brazilin inhibits amyloid β-protein fibrillogenesis, remodels amyloid fibrils and reduces amyloid cytotoxicity, Sci. Rep., 2015, 5, 7992.

- J. Guo, W. Sun, L. Li, F. Liu, W. Lu, Brazilin inhibits fibrillogenesis of human islet amyloid polypeptide, disassembles mature fibrils, and alleviates cytotoxicity, R.S.C. Adv., 2017, 7, 43491-43501.

- R.I. Jenie, S. Handayani, R.A. Susidarti, L.Z. Udin, E. Meiyanto, The cytotoxic and anti-migratory activity of brazilin-doxorubicin on MCF-7/HER2 cells, Adv. Pharm. Bull., 2018, 8, 507-516.

- N.P.L. Laksmiani, E.D.Y. Meiyanto, R.A. Susidarti, Cytotoxic activity of brazilein isolated from Secang (Caesalpinia sappan L.) against MCF7/DOX cells by inhibition of P-glycoprotein, Int. J. Pharm. Pharm. Sci., 2017, 9, 124-130.

- M. Li, X. Dong, Y. Liu, Y. Sun, Brazilin Inhibits Prostatic Acidic Phosphatase Fibrillogenesis and Decreases its Cytotoxicity, Chem. Asian J., 2017, 12, 1062-1068.

- F. Liu, Y. Wang, J. Sang, W. Wei, W. Zhao, B. Chen, F. Zhao, L. Jia, F. Lu, Brazilin Inhibits α-Synuclein Fibrillogenesis, Disrupts Mature Fibrils, and Protects against Amyloid-Induced Cytotoxicity, J. Agric. Food Chem., 2019, 67, 11769-11777.

- C. Ngernnak, P. Panyajai, S. Anuchapreeda, W. Wongkham, A. Saiai, Phytochemical and cytotoxic investigations of the heartwood of Caesalpinia sappan linn, Asian J. Pharm. Clin. Res., 2018, 11, 1-4.

- C.C. Lee, C.N. Wang, J.J. Kang, J.W. Liao, B.L. Chiang, H.C. Chen, C.M. Hu, C.D. Lin, S.H. Huang, Y.T. Lai, Antiallergic Asthma Properties of Brazilin through Inhibition of TH2 Responses in T Cells and in a Murine Model of Asthma, J. Agric. Food Chem., 2012, 60, 9405-9414.

- S.R. Oh, D.S. Kim, I.S. Lee, K.Y. Jung, J.J. Lee, H.-K. Lee, Anticomplementary activity of constituents from the heartwood of Caesalpinia sappan, Planta Med., 1998, 64, 456-458.

- C.-M. Hu, Y.-H. Liu, K.-P. Cheah, J.-S. Li, C.-S.K. Lam, W.-Y. Yu, C.-S. Choy, Heme oxygenase-1 mediates the inhibitory actions of brazilin in RAW264.7 macrophages stimulated with lipopolysaccharide, J. Ethnopharmacol., 2009, 121, 79-85.

- M. Washiyama, Y. Sasaki, T. Hosokawa, S. Nagumo, Anti-inflammatory constituents of Sappan Lignum, Biol. Pharm. Bull., 2009, 32, 941-944.

- C.M. Hu, J.J. Kang, C.C. Lee, C.H. Li, J.W. Liao, Y.W. Cheng, Induction of vasorelaxation through activation of nitric oxide synthase in endothelial cells by Brazilin, Eur. J. Pharmacol., 2003, 468, 37-45.

- Y. Sasaki, M. Suzuki, T. Matsumoto, T. Hosokawa, T. Kobayashi, K. Kamata, S. Nagumo, Vasorelaxant activity of Sappan Lignum constituents and extracts on rat aorta and mesenteric artery, Biol. Pharm. Bull., 2010, 33, 1555-1560.

- Y.W. Xie, D.S. Ming, H.X. Xu, H. Dong, P.P.H. But, Vasorelaxing effects of Caesalpinia sappan. Involvement of endogenous nitric oxide, Life Sci., 2000, 67, 1913-1918.

- Y. Yan, Y.C. Chen, Y.H. Lin, J. Guo, Z.R. Niu, L.H. Fang, L. Li, S.B. Wang, G.H. Du, Brazilin isolated from the heartwood of Caesalpinia sappan L induces endothelium-dependent and -independent relaxation of rat aortic rings, Acta Pharmacol. Sin., 2015, 36, 1318-1326.

- H.S. Won, J. Lee, L.Y. Khil, S.H. Chae, M.Y. Ahn, B.H. Lee, J.H. Chung, Y.C. Kim, C.K. Moon, Mechanism of action of brazilin on gluconeogenesis in isolated rat hepatocytes, Planta Med., 2004, 70, 740-744.

- E.J. You, L.Y. Khil, W.J. Kwak, H.S. Won, S.H. Chae, B.H. Lee, C.K. Moon, Effects of brazilin on the production of fructose-2,6-bisphosphate in rat hepatocytes, J. Ethnopharmacol., 2005, 102, 53-57.

- G.M. Uddin, C.Y. Kim, D. Chung, K.-A. Kim, S.H. Jung, One-step isolation of sappanol and brazilin from Caesalpinia sappan and their effects on oxidative stress-induced retinal death, B.M.B. Rep., 2015, 48, 289-294.

- P. Pfeiffer, P. Schneider, Quinoid oxidation products in the brasilin series, J. Prakt. Chem. (Leipzig), 1935, 144, 54-62.

- R. Robinson, Chemistry of brazilin and hematoxylin, Bull. Soc. Chim. Fr., 1958, 1, 125-134.

- D.S. Kim, N.I. Baek, S.R. Oh, K.Y. Jung, I.S. Lee, H.K. Lee, N.M.R. assignment of Brazilein, Phytochemistry, 1997, 46, 177-178.

- L.F.C. de Oliveira, H.G.G.M. edwards, E.S. Velozo, M. Nesbitt, Vibrational spectroscopic study of brazilin and brazilein, the main constituents of brazilwood from Brazil, Vibrat. Spectrosc., 2002, 28, 243-249.

- R. Csuk, A. Barthel, R. Sczepek, B. Siewert, S. Schwarz, Synthesis, Encapsulation and Antitumor Activity of New Betulin Derivatives, Arch. Pharm., 2011, 344, 37-49.

- L. Heller, A. Knorrscheidt, F. Flemming, J. Wiemann, S. Sommerwerk, I.Z. Pavel, A. Al-Harrasi, R. Csuk, Synthesis and proapoptotic activity of oleanolic acid derived amides, Bioorg. Chem., 2016, 68, 137-151.

- S. Sommerwerk, L. Heller, J. Kuhfs, R. Csuk, Selective killing of cancer cells with triterpenoic acid amides - The substantial role of an aromatic moiety alignment, Eur. J. Med. Chem., 2016, 122, 452-464.

- R.H. Jaeger, P.M.E. Lewis, R. Robinson, Reduction of brazilein. Occurrence of reductive coupling, Tetrahedron, 1974, 30, 1295-1300.

- R. Csuk, B. Siewert, C. Dressel, R. Schäfer, Tormentic acid derivatives: synthesis and apoptotic activity, Eur. J. Med. Chem., 2012, 56, 237-245.

- L.-G. Lin, H. Xie, H.-L. Li, L.-J. Tong, C.-P. Tang, C.-Q. Ke, Q.-F. Liu, L.-P. Lin, M.-Y. Geng, H. Jiang, W.-M. Zhao, J. Ding, Y. Ye, Naturally Occurring Homoisoflavonoids Function as Potent Protein Tyrosine Kinase Inhibitors by c-Src-Based High-Throughput Screening, J. Med. Chem., 2008, 51, 4419-4429.

- R.B. Irby, T.J. Yeatman, Role of Src expression and activation in human cancer, Oncogene, 2000, 19, 5636-5642.

- L.D. Lavis, Ester Bonds in Prodrugs, A.C.S. Chem. Biol., 2008, 3, 203-206.

- C.B. Breitenlechner, N.A. Kairies, K. Honold, S. Scheiblich, H. Koll, E. Greiter, S. Koch, W. Schäfer, R. Huber, R.A. Engh, Crystal Structures of Active Src Kinase Domain Complexes, J. Mol. Biol., 2005, 353, 222-231.

- M.M. Massip Copiz, T.A. Santa Coloma, c- Src and its role in cystic fibrosis, European J. Cell Biol., 2016, 95, 401-413.

- Y. Niu, S. Wang, C. Li, J. Wang, Z. Liu, W. Kang, Effective compounds from Caesalpinia sappan L. on the tyrosinase in vitro and in vivo, Nat. Prod. Commun., 2020, 15, 1934578X20920055.

- M. Sudhakar, P. Krishnaiah, A.L. Rao, D.B. Raju, Antimicrobial guided phytochemical evaluation of the pods of Caesalpinia pulcherrima, Asian J. Chem., 2005, 17, 2353-2358.

- W. Mar, H.T. Lee, K.H. Je, H.Y. Choi, E.K. Seo, A DNA strand-nicking principle of a higher plant, Caesalpinia sappan, Arch. Pharmacal Res., 2003, 26, 147-150.

- K. Buchka, A. Erck, Beiträge zur Kenntnis des Brasilins, Ber. Deutsch. Chem. Ges., 1885, 18, 1138-1143.

- W.J. Kwak, M.H. Kim, S.D. Jeon, L.Y. Khil, S.H. Chae, D. Kim, B.H. Lee, C.K. Moon, Effects of Brx-019 (acetic acid 3,6a,9-triacetoxy-6,6a,7,11b-tetrahydro-indeno [2,1-c]chromen-10-yl ester), a Brazilin derivative, on T cell-mediated immune responses in multiple low dose streptozotocin-induced diabetic C57BL/6 male mice, Arzneimittelforschung, 2005, 55, 541-548.

- J. Herzig, J. Pollak, R. Fischer, W. Kluger, A. Mayrhofer, Über Brasilin und Hämatoxylin, Monatsh. Chem., 1906, 27, 743-771.




DOI: http://dx.doi.org/10.13171/mjc10802010061536rc

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