Synthesis and Cytotoxic Evaluation of 3-Dimethyl Carbamoyl Emodin

Firdayani Firdayani, Shelvi Listiana, Billy Witanto


Emodin (6-methyl-1,3,8-trihydroxyanthraquinone) is a natural anthraquinone derivative with potential pharmacological such as cytotoxic effects. The structure modification could be performed to determine the functional groups that have the role of substance activities. In this study, we modified one hydroxy group in the emodin structure to become dimethyl carbamoyl moiety. Emodin was reacted with dimethyl carbamoyl chloride and potassium carbonate to create 3-dimethyl carbamoyl emodin. The structure of the product was elucidated using mass spectrophotometer (MS), Fourier transform infrared (FTIR), proton and carbon nuclear magnetic resonance (H-NMR and C-NMR). These substances were tested for cytotoxicity against HepG2 cell lines using the MTT assay. According to the evaluation, 3-dimethyl carbamoyl emodin is less cytotoxic than emodin. As a result, the hydroxy group at the C3 position of emodin has been identified as a functional component that contributes to its cytotoxic effect.


carbamoyl; cytotoxic; emodin; HepG2


Zibaee, E., Javadi, B., Sobhani, Z., Akaberi, M., Farhadi, F., Amiri, M. S., Baharara, H., Sahebkar, A., & Emami, S. A. (2023). Cassia species: A review of traditional uses, phytochemistry and pharmacology. Pharmacological Research - Modern Chinese Medicine, 9, 100325.

Sun, Y., Lenon, G. B., & Yang, A. W. H. (2020). Rumex japonicus Houtt.: A phytochemical, pharmacological, and pharmacokinetic review. In Phytotherapy Research (Vol. 34, Issue 6, pp. 1198–1215). John Wiley and Sons Ltd.

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.

Sharifi-Rad, J., Herrera-Bravo, J., Kamiloglu, S., Petroni, K., Mishra, A. P., Monserrat-Mesquida, M., ... & Cho, W. C.(2004) Recent advances in the therapeutic potential of emodin for human health. Biomedicine & Pharmacotherapy, 154, 113555

Tuli, H. S., Aggarwal, V., Tuorkey, M., Aggarwal, D., Parashar, N. C., Varol, M., Savla, R., Kaur, G., Mittal, S., & Sak, K. (2021). Emodin: A metabolite that exhibits anti-neoplastic activities by modulating multiple oncogenic targets. In Toxicology in Vitro (Vol. 73). Elsevier Ltd.

Stompor-Gorący, M. (2001).The health benefits of emodin, a natural anthraquinone derived from rhubarb—a summary update. International Journal of Molecular Sciences, 22(17), 9522.

Zheng, Q., Li, S., Li, X., & Liu, R. (2021). Advances in the study of emodin: an update on pharmacological properties and mechanistic basis. Chinese Medicine, 16, 1-24.

Wang, X., Yang, S., Li, Y., Jin, X., Lu, J., & Wu, M. (2023). Role of emodin in atherosclerosis and other cardiovascular diseases: Pharmacological effects, mechanisms, and potential therapeutic target as a phytochemical. In Biomedicine and Pharmacotherapy (Vol. 161). Elsevier Masson s.r.l.

Subramaniam, A., Loo, S. Y., Rajendran, P., Manu, K. A., Perumal, E., Li, F., Shanmugam, M. K., Siveen, K. S., Park, J. I., Ahn, K. S., Hui, K. M., Kumar, A. P., & Sethi, G. (2013). An anthraquinone derivative, emodin sensitizes hepatocellular carcinoma cells to TRAIL induced apoptosis through the induction of death receptors and downregulation of cell survival proteins. Apoptosis, 18(10), 1175–1187.

Shu, S.C. and . Chung, J.G, 2012. Anticancer potential of emodin. BioMedicine,. 2(3): p. 108-116.

D’Souza, M. J., & Kevill, D. N. (2016). Mechanistic studies of the solvolyses of carbamoyl chlorides and related reactions. In International Journal of Molecular Sciences (Vol. 17, Issue 1). MDPI AG.

Firdayani, F., Nuralih, N., Kusumastuti, S. A., & Hasan, H..(2002) Acetylation of Emodin and Cytotoxic Activity Effect Against HepG2 Cell Lines. In Proceedings of International Pharmacy Ulul Albab Conference and Seminar (PLANAR) (Vol. 2, pp. 38-44).

Jäger, P., Rentzea, C. N., & Kieczka, H. (2000). Carbamates and Carbamoyl Chlorides. In Ullmann’s Encyclopedia of Industrial Chemistry. Wiley.

Dallaire, C., Kolber, I., and Gingras,. M. (2003) Nickel-Catalyzed Coupling of Aryl O-Carbamates With Grignard Reagents: 2,7-Dimethylnaphthalene. Organic Syntheses: p. 42-42

Sassa Osamu Sugita Richard Galbraith, S. A., & Kappas, A. (1987). Drug Metabolism by The Bullbb Hbpatolia Cell, Bep G2 (Vol. 143, Issue 1).

Huang, T., Huang, Y., Huang, Y., Yang, Y., Zhao, Y., & Martyniuk, C. J. (2020). Toxicity assessment of the herbicide acetochlor in the human liver carcinoma (HepG2) cell line. Chemosphere, 243.

Majer, B. J., Mersch-Sundermann, V., Darroudi, F., Laky, B., De Wit, K., & Knasmüller, S. (2004). Genotoxic effects of dietary and lifestyle related carcinogens in human derived hepatoma (HepG2, Hep3B) cells. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 551(1–2), 153–166.

Patrick, G.L., (2013). An introduction to medicinal chemistry: Oxford University Press.

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DOI: 10.15408/jkv.v9i2.34654


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