Acetylation of Emodin and Cytotoxic Activity Effect Against HepG2 Cell Lines

Firdayani Firdayani; Nuralih Nuralih; Siska Andrina Kusumastuti; Hasan Hasan

doi:10.18860/planar.v2i0.1858

Firdayani Firdayani Badan Riset dan Inovasi Nasional http://orcid.org/0000-0001-9967-917X
Nuralih Nuralih Badan Riset dan Inovasi Nasional http://orcid.org/0000-0001-9145-2093
Siska Andrina Kusumastuti Badan Riset dan Inovasi Nasional http://orcid.org/0000-0002-6270-3356
Hasan Hasan Badan Riset dan Inovasi Nasional

DOI: https://doi.org/10.18860/planar.v2i0.1858

Abstract

Emodin (1,3,8-trihydroxy-6-methyl-9,10-anthraquinone) is an anthraquinone bioactive compound used as a lead compound because it exhibits potential anticancer properties. Structural modifications were made at the C3 position and its relationship to cytotoxic activity against the HepG2 cell line to determine the pharmacophore group of this compound. The hydroxy group at C3 emodin is converted to an ester group to produce 3-acetyl emodin. In addition, docking simulations into the cancer target protein casein kinase-2 were also carried out to predict molecular interactions. Emodin was reacted with anhydrous acetate and confirmed the product confirmation using LCMS/MS, FTIR, ¹H-NMR, and ¹³C-NMR. Emodin and 3-acetyl emodin were tested for cytotoxicity against HepG2 cells in vitro. Cytotoxic emodin and 3-acetyl emodin tests on HepG2 cells resulted in Cytotoxic concentrations 50 (CC₅₀) of 0.54 mM and 0.42 mM, respectively. The results showed that modifying the C3 hydroxyl group with acetyl can increase the cytotoxic effect more than emodin. This research is expected to provide information regarding the structure-activity relationship of emodin in cancer cells and the expansion of new drug applications for additional cancers.

References

Dong, X., Fu, J., Yin, X., Cao, S., Li, X., Lin, L., et al. (2016). Emodin: A Review of its Pharmacology, Toxicity and Pharmacokinetics. Phytotherapy Research, 30(8), 1207-1218. https://doi.org/10.1002/ptr.5631
Frantík, T., Kovářová, M., Koblihová, H., Bartůňková, K., Nývltová, Z., & Vosátka, M. (2013). Production of medically valuable stilbenes and emodin in knotweed. Industrial Crops and Products, 50, 237-243. https://doi.org/10.1016/j.indcrop.2013.07.017
Guo, S., Feng, B., Zhu, R., Ma, J., & Wang, W. (2011). Preparative isolation of three anthraquinones from Rumex japonicus by high-speed counter-current chromatography. Molecules, 16(2), 1201-1210. https://doi.org/10.3390/molecules16021201
Hevener, K. E., Zhao, W., Ball, D. M., Babaoglu, K., Qi, J., White, S. W., et al. (2009). Validation of molecular docking programs for virtual screening against dihydropteroate synthase. Journal of Chemical Information and Modeling, 49(2), 444-460. https://doi.org/10.1021/ci800293n
Hsu, S. C. & Chung, J. G. (2012). Anticancer potential of emodin. Biomedicine, 2(3), 108-116. https://doi.org/10.1016/j.biomed.2012.03.003
Janeczko, M., Masłyk, M., Kubiński, K., & Golczyk, H. (2017). Emodin, a natural inhibitor of protein kinase CK2, suppresses growth, hyphal development, and biofilm formation of Candida albicans. Yeast, 34(6), 253-265. https://doi.org/10.1002/yea.3230
Clayden, J., Greeves, N., & Warren, S. (2012). Organic Chemistry Second Edition. New York: Oxford University Press.
Kristanti, A. N., Amina, N. S., & Tanjung, M. (2010). Isolasi Senyawa Antrakuinon dari Cassia multijuga (Leguminosae). Jurnal Kimia Indonesia, 1(1), 17.
Lipinski, C. A. (2004). Lead-and drug-like compounds: the rule-of-five revolution. Drug Discovery Today: Technologies, 1(4), 337-341. https://doi.org/10.1016/j.ddtec.2004.11.007
Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of Immunological Methods, 65(1-2), 55-63. https://doi.org/10.1016/0022-1759(83)90303-4
Sarno, S., Moro, S. M., Meggio, F., Zagotto, G., Ben, D. D., Ghisellini, P., et al. (2002). Toward the rational design of protein kinase casein kinase-2 inhibitors. Pharmacology & Therapeutics, 93(2), 159-168. https://doi.org/10.1016/s0163-7258(02)00185-7
Siswandono. (2016). Kimia Medisinal Jilid Satu (2nd edition). Surabaya: Universitas Airlangga.
Teich, L., Daub, K. S., Krügel, V., Nissler, L., Gebhardt, R., & Eger, K. (2004). Synthesis and biological evaluation of new derivatives of emodin. Bioorganic and Medicinal Chemistry, 12(22), 5961-5971. https://doi.org/10.1016/j.bmc.2004.08.024
Thomsen, R. & Christensen, M. H. (2006). MolDock: a new technique for high-accuracy molecular docking. Journal of Medicinal Chemistry, 49(11), 3315-3321. https://doi.org/10.1021/jm051197e