• Vasyl I. Shupeniuk Vasyl Stefanyk Precarpathian National University, Ukraine
  • Tetyana N. Taras Precarpathian National University. V. Stefanyk, Ukraine
  • Oksana P. Sabadakh Precarpathian National University. V. Stefanyk, Ukraine
  • Evgeny R. Luchkevich Precarpathian National University. V. Stefanyk, Ukraine
  • Nikolay P. Matkivsky Precarpathian National University. V. Stefanyk, Ukraine



1(2)-гідроксиантрахінон; фталевий ангідрид; реакція Дільса-Альдера; реакція Фріделя-Крафтса; діазотування; протипухлинна активність; токсичність


Hydroxyanthraquinones are active components of many traditional medicinal plants, including Cassia acutifolia, Rhamnus frangula, Rheum rhabarbarum, Aloe vera. For the first time, the methods of obtaining synthetic derivatives of hydroxyanthraquinone are generalized and the spectrum of their biological activity and toxic effect on the human body is described. Some hydroxyanthraquinone derivatives have shown potential in the treatment of acute pathological conditions. The review is devoted to the synthesis of hydroxyanthraquinone derivatives obtained by reactions of Friedel-Crafts, Diels-Alder, nucleophilic substitution, diazotization, cycloaddition according to the publications of the SciFinder and Reaxys databases for the last 20 years. The first methods of industrial production of hydroxyanthraquinone were the catalytic oxidation of anthracene obtained from coal tar. Derivatives of phthalic anhydride and phenol were most often used as starting materials for obtaining hydroxy groups in the anthraquinone ring. Hydroxy derivatives of the anthraquinone series were obtained as by-products in the reactions of Zandmeyer, Ullmann, Meyerwein and others described in the review.

Author Biographies

Vasyl I. Shupeniuk, Vasyl Stefanyk Precarpathian National University

інженер кафедри хімії середовища та хімічної освіти

Tetyana N. Taras, Precarpathian National University. V. Stefanyk

завідуюча кафедрою 

кандидат хімічних наук, доцент 


Gessler, N.N.; Egorova, A.S.; Belozerskaya, T.A. (2013). Fungal anthraquinones. Appl Biochem Microbiol. 49(2), 85–99.

Pankewitz, F.; Zoёllmer, A.; Graёser, Y.; Hilker, M. (2007). Anthraquinones as defensive compounds in eggs ofGalerucini leaf beetles: Biosynthesis by the beetles? Arch Insect Biochem Physiol. 66(2), 98–108.

Malik, E.; Muller, C. (2016). Anthraquinones As Pharmacological Tools and Drugs. Medicinal research reviews. 36(4), 705-748.

Alaadin, A.M.; Al-Khateeb, E.H.; J¨ager, A.K. (2007). Antibacterial activity of the Iraqi Rheum ribes. Root. Pharm. Biol. 45(9), 688–690.

Huang, Q.; Lu, G.; Shen, H.M.; Chung, M.; Ong, C.N. (2007). Anti-cancer properties of anthraquinones from rhubarb. Med. Res. Rev. 27(5), 609–630.

Marzouk, B.; Marzouk, Z.; D´ecor, R.; (2009). Antibacterial and anticandidal screening of Tunisian Citrullus colocynthis Schrad. from Medenine. J. Ethnopharmacol. 125(2), 344–349.

Osman, C.P.; Ismail, N.H.; Ahmad, R.; Ahmat, N.; Awang, K.; Jaafar, F.M. (2010). Anthraquinones with antiplasmodial activity from the roots of Rennellia elliptica Korth. (Rubiaceae). Molecules. 15(10), 7218–7226.

Achmad, F.H.; Aty, W.; Arannya, P.D.; Nike, F.; Lidya, T.; Indah, S.T. (2014). In vitro antimalarial activity screening of several Indonesian plants using HRP2 assay. Int. J. Pharm. Pharm. Sci. 6, 125–128.

Kingwell, E.; Koch, M.; Leung, B.; Isserow, S.; Geddes, J.; Rieckmann, P.; Tremlett, H. (2010). Cardiotoxicity and other adverse events associated with mitoxantrone treatment for MS. Neurology. 74(22), 1822–1826. DOI:

Hussain, H.; Al-Harrasi, A.; Al-Rawahi, A.; Green, I.; Csuk, R.; Ahmed, I.; Shan, A.; Abbas, G.; Rehman, N.; Ullah, R. (2015). A fruitful decade from 2005 to 2014 for anthraquinone patents. Expert Opin. Ther. Patents. 1053-1064.

Khanal, P.; Patil, B. M.; Chand, J.; Naaz, Y. (2020). Anthraquinone Derivatives as an Immune Booster and their Therapeutic Option Against COVID-19. Natural Products and Bioprospecting. 10, 325-335.

Boisvert, L.; Brassard, P. (1988). Regiospecific addition of monooxygenated dienes to halo quinines. J. Org. Chem. 53, 4052-4059.

Godleski, S.; Valpey, R. (1982). Novel oxidative transformation: regiospecific preparation of naturally occurring 1-hydroxyanthraquinones. J. Org. Chem. 47, 383-384.

Zembower, D.; Kam, C.-M.; Powers, J.; Zalkow, L. (1992). Novel anthraquinone inhibitors of Human Leukocyte Elastase and Cathepsin G1. J. Med. Chem. 35, 1597-1605.

Komiyama, T.; Takaguchi, Y.; Tsuboi, S. (2006). Synthesis of anthraquinone derivatives: tandem Diels–Alder-Decarboxylation–Oxidation reaction of 3-hydroxy-2-pyrone with 1,4-naphthoquinone. SYNLETT. 1, 124–126. DOI: 10.1055/s-2005-922769

Dhananjeyan, M.R.; Milev, Y.P.; Kron, M.A.; Nair, M.G. (2005). Synthesis and activity of substituted anthraquinones against a human filarial parasite, Brugia malayi. J. Med. Chem. 48, 2822−2830.

Ye, M.-Y; Yao, G.-Y.; Pan, Y.-M.; Liao, Z.-X.; Zhang, Y.; Wang, H.-S. (2014). Synthesis and antitumor activities of novel a-aminophosphonate derivatives containing an alizarin moiety. European Journal of Medicinal Chemistry. 83, 116-128.

Zhang, Z.; Li, X.; Song, T.; Zhao, Y.; Feng, Y. (2012). An anthraquinone scaffold for putative, Two-Face Bim BH3 α‑Helix Mimic. J. Med. Chem. 53(23), 10735−10741.

Gupta, R.; Thakuri, G.; Bajracharya, G.; Jha, R. N. (2021). Synthesis of antioxidative anthraquinones as potential anticancer agents. BIBECHANA. 18(2), 143-153.

Shupeniuk, V.; Taras, T.; Sabadakh, O.; Luchkevich, E.; Matkivsky, N. (2020). Synthesis of nitrogen-containing heterocyclic compounds based on 9,10-anthraquinone derivatives. Journal of Chemistry and Technologies. 28(2), 122-132. DOI:

Sabadakh, O.P.; Taras, T.M.; Luchkevich, E.R.; Novikov, V.P. (2015). Synthesis of triazene derivatives of 9, 10-anthraquinone. Russ. J. Org. Chem. 51(2), 277-278.

Shupeniuk, V.I.; Amaladoss, N.; Taras, T.N.; Sabadakh, O.P.; Matkivskyi, N.P. (2021). Synthesis and In Silico Study of 4-Substituted 1-Aminoanthraquinones. Russ. J. Org. Chem. 57, 582-588.

Blankespoor, R.; Smart, R.; Batts, E.; Kiste, A.; Lew, R.; Vliet, M. (1995). Photochemistry of l-alkoxy- and l-(benzyloxy)-9,10-anthraquinones in methanol: A facile process for the preparation of aldehydes and ketones. J. Org. Chem. 60, 6852-6859.

Yoshida, K.; Hikasa, M.; Ishii. K.; Kadota, H.; Yamashita, Y. (1986). Salective photoalkylamination and photohydroxylation of aminoanthraquinones and their N-acylated derivatives. J. Chem. Soc., Chem. Commun. 10, 758-759.

Tkachenko, T.B. The reactions of aminoanthraquinones of anthraquinonyl diazonium salts, accompanied by a complication of the carbon skeleton. Abstract of the dissertation for the degree of candidate of chemical sciences: specialty 02.00.03 “Organic chemistry”. Kemerovo State University, Tomsk, 2005.

Denisov, V.; Tkachenko, T. (2005). Investigation of the reactions of anthraquinonyl diazonium salts. Izvestiya Vysshikh Uchebnykh Zavedenii, Seriya “Khimiya I Khimicheskaya Tekhnologiya”. 48, 99.

Taras, T. M.; Dejchakivsky, Y. I.; Shupeniuk, V. I.; Sabadakh, O. P.; Bolibrukh, L. D. (2019). Features of obtaining triazens of the anthraquinone series. Chem., Technol. and Application of Substances. 2(1), 92.

Inoue, H.; Hida, M.; Tuong, T.D.; Murata, T. (1973). The Nucleophilic Photo-substitution reaction of anthraquinone derivatives. I. The Photo-amination of sodium 1-amino-4-bromanthraquinone-2-sulfate. J. Chem. Soc., of Japan, 46, 1759 - 1762.

Smart, R.; Peelen, T.; Blankespoor, R.; Ward, D. (1997). Short-Lived 1,5-biradicals formed from triplet 1-alkoxy- and 1-(benzyloxy)-9,10-anthraquinones. J. Am. Chem. Soc. 119, 461-465.

Blankespoor, R.; De Jong, R.; Dykstra, R.; Hamstra, D.; Rozema, D.; Van Meurs, D.; Vink, P. (1991). Photochemistry of 1-alkoxy- and 1-(benzyloxy)-9,l0-anthraquinones in methanol: A hydrogen atom abstraction process that exhibits a captodative effect. J. Am. Chem. Soc. 113, 3507-3513.

Kappe, C.O.; Dallinger, D. (2009). Controlled microwave heating in modern organic highlights from the 2004-2008. Mol. Divers. 13, 171–193.

Patricci, E.; Mann, A.; Schoenfelder, A. (2006). Microwaves Make Hydroformylation a Rapid and Easy Process. Org. Lett. 8(17), 3725-3727.

Baqi, Y.; Muller, C.E. (2010). Synthesis of alkyl- and aryl-amino-substituted anthraquinone derivatives by microwave-assisted copper (0)-catalyzed Ullmann coupling reactions. Nature Protocol. 5(5), 387-390. doi:10.1038/nprot.2010.63

Patel, K.; Gadewar, M.; Tahilyani, V.; Patel, D.K. (2012). Barbaloin: A concise report of its pharmacological and analytical aspects. Asian Pac J Trop Biomed. 2(10), 835–838. DOI 10.1007/s13659-012-0014-3

Kumar, G.D.; Siva, B.; Vadlamudi, S.; Bathula, S.R.; Duttad, H.; Babu, K.S. (2021). Design, synthesis, and biological evaluation of pyrazole-linked aloe emodin derivatives as potential anticancer agents. Advance Article. DOI: 10.1039/D0MD00315H

Wang, C.; Zhang, D.; Ma, H.; Liu, J. (2007). Neuroprotective effects of emodin-8-O-beta-D-glucoside in vivo and in vitro. Eur J Pharmacol. 577, 58–63.

Yu, C.; Qi, D.; Sun, J-F.; Li, P.; Fan, H-Y. (2015). Rhein prevents endotoxin-induced acute kidney injury by inhibiting NF-κB activities. Sci Rep. 5, 11822.

Wald, A. (2003). Is chronic use of stimulant laxatives harmful to the colon?. J Clin Gastroenterol. 36(5), 386–389.

Kushi, L.H.; Doyle, C.; McCullough, M.; Rock, C.L.; Demark-Wahnefried, W.; Bandera, E.V.; Gapstur, S.; Patel, A.V.; Andrews, K.; Gansler, T. (2012). American Cancer Society guidelines on nutrition and physical activity for cancer prevention. CA Cancer J. Clin. 62(1), 30–67. doi:10.3322/caac.20140

Helleday, T.; Petermann, E.; Lundin, C.; Hodgson, B.; Sharma, R.A. (2008). DNA repair pathways as targets for cancer therapy. Nat. Rev. Cancer. 8(3), 193-204. DOI:10.1038/nrc2342

Xing, J-y.; Song, G-p.; Deng, J-p.; Jiang, L.-z.; Xiong, P., Yang, B.-j.; Liu S.-s. (2015). Antitumor effects and mechanism of novel emodin rhamnoside derivatives against human cancer cells in vitro. PLoS ONE. 10(12), e0144781.

Han, Y-M.; Lee, S-K.; Jeong, D.G.; Ryu, S.E.; Han, D.C.; Kim, D.K.; Kwon B-M. (2012). Emodin inhibits migration and invasion of DLD-1 (PRL-3) cells via inhibition of PRL-3 phosphatase activity. Bioorg. Med. Chem. Lett. 22(1), 323–326.

Greco, G.; Turrini, E.; Catanzaro, E.; Fimognari C. (2021). Marine Anthraquinones: Pharmacological and Toxicological Issues. Marine drugs. 19(5), 272. DOI: 10.3390/md19050272

Siddamurthi, S.; Gutti, G.; Jana, S.; Kumar, A.; Singh, S.K. (2020). Anthraquinone: a promising scaffold for the discovery and development of therapeutic agents in cancer therapy. Future medicinal chemistry. 12(11), 1037-1069. DOI: 10.4155/fmc-2019-0198

Tan, Q.-W.; Ouyang, M.-A.; Shen, S.; Li, W. (2012). Bioactive Metabolites from a Marine-Derived Strain of the Fungus Neosartorya Fischeri. Nat. Prod. Res. 26, 1402–1407. doi:10.3390/md13031569

Jelassi, B.; Anchelin, M.; Chamouton, J.; Cayuela, M.L.; Clarysse, L.; Li, J.; Goreґ, J.; Jiang, L-H.; Roger, S. (2013). Anthraquinone emodin inhibits human cancer cell invasiveness by antagonizing P2x7 receptors. Carcinogenesis. 34(7), 1487–1496.

Ma, Y.S.; Weng, S.W.; Lin, M.W.; Lu, C.C.; Chiang, J.H.; Yang, J.S.; Lai, K.C.; Lin, J.P.; Tang, N.Y.; Lin, J.G.; Chung, J.G. (2012). Antitumor effects of emodin on LS1034 human colon cancer cells in vitro and in vivo: Roles of apoptotic cell death and LS1034 tumor xenografts model. Food Chem Toxicol. 50(5), 1271–1278.

Lin, S.Z.; Wei, W.T.; Chen, H.; Chen, K.J.; Tong, H.F.; Wang, Z.H.; Ni, Z.L.; Liu, H.B.; Guo, H.C.; Liu, D.L. (2012). Antitumor activity of emodin against pancreatic cancer depends on its dual role: Promotion of apoptosis and suppression of angiogenesis. PLoS One. 7(8), 1–15.

Pecere, T.; Gazzola, M.V.; Mucignat, C.; Tumors, N.; Parolin, C.; Vecchia, F.D.; Cavaggioni, A.; Basso, G.; Diaspro, A.; Salvato, B.; Carli, M.; Palu, G. (2000). Aloe-emodin is a new type of anticancer agent with selective activity against neuroectodermal tumors advances in brief aloe-emodin is a new type of anticancer agent with selective activity against neuroectodermal tumors. Cancer Res. 60, 2800–2804.

Kuo, P-L.; Lin, T-C.; Lin, C-C. (2002). The antiproliferative activity of aloe-emodin is through p53-dependent and p21-dependent apoptotic pathway in human hepatoma cell lines. Life Sci. 71(16), 1879–1892.

Guo, J.; Xiao, B.; Liu, Q.; Zhang, S.; Liu, D.; Gong, Z. (2007). Anticancer effect of aloe-emodin on cervical cancer cells involves G2/M arrest and induction of differentiation. Acta Pharmacol Sin. 28(12), 1991–1995. doi: 10.1111/j.1745-7254.2007.00707.x

Chiu, T.H.; Lai, W.W.; Hsia, T.C.; Yang, J.S.; Lai, T.Y.; Wu, P.P.; Ma, C.Y.; Yeh, C.C.; Ho, C.C.; Lu, H.F.; Wood, W.G.; Chung, J.G. (2009). Aloe-emodin induces cell death through S-phase arrest and caspase-dependent pathways in human tongue squamous cancer SCC-4 cells. Anticancer Res. 29(11), 4503–4511.

Bottenberg, M.M.; Wall, G.C.; Harvey, R.L.; Habib, S. (2007). Oral aloe vera-induced hepatitis. Ann Pharma-cother. 41(10), 1740–1743.

World Health Organization International Agency for Research on Cancer. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene, and Styrene. 2002. p. 129–151.

National Toxicology Program. TR-493. Toxicology and carcinogenesis studies of emodin (CASNO. 518-82-1) feed studies in F344/N rats and B6C3F1 mice. Natl Toxicol Program Tech Rep Ser. 2001. 493, 1–278.