A Review on Shikonin and its Derivatives as Potent Anticancer Agents Targeted against Topoisomerases
- Authors: Olatunde O.1, Yong J.2, Lu C.3, Ming Y.4
-
Affiliations:
- Fujian Institute of Research on the Structure of Matte, Chinese Academy of Sciences
- Xiamen Institute of Rare-earth Materials, Chinese Academy of Sciences
- Fujian Institute of Research on the Structure of Matter,, Chinese Academy of Sciences
- , Fujian Institute of Subtropical Botany
- Issue: Vol 31, No 8 (2024)
- Pages: 920-937
- Section: Anti-Infectives and Infectious Diseases
- URL: https://rjpbr.com/0929-8673/article/view/645189
- DOI: https://doi.org/10.2174/0929867330666230208094828
- ID: 645189
Cite item
Full Text
Abstract
The topoisomerases (TOPO) play indispensable roles in DNA metabolism, by regulating the topological state of DNA. Topoisomerase I and II are the well-established drug-targets for the development of anticancer agents and antibiotics. These drugs-targeting enzymes have been used to establish the relationship between drug-stimulated DNA cleavable complex formation and cytotoxicity. Some anticancer drugs (such as camptothecin, anthracyclines, mitoxantrone) are also widely used as Topo I and Topo II inhibitors, but the poor water solubility, myeloma suppression, dose-dependent cardiotoxicity, and multidrug resistance (MDR) limited their prolong use as therapeutics. Also, most of these agents displayed selective inhibition only against Topo I or II. In recent years, researchers focus on the design and synthesis of the dual Topo I and II inhibitors, or the discovery of the dual Topo I and II inhibitors from natural products. Shikonin (a natural compound with anthraquinone skeleton, isolated from the roots of Lithospermum erythrorhizon) has drawn much attention due to its wide spectrum of anticancer activities, especially due to its dual Topo inhibitive performance, and without the adverse side effects, and different kinds of shikonin derivatives have been synthesized as TOPO inhibitors for the development of anticancer agents. In this review, the progress of the shikonin and its derivatives together with their anticancer activities, anticancer mechanism, and their structure-activity relationship (SAR) was comprehensively summarized by searching the CNKI, PubMed, Web of Science, Scopus, and Google Scholar databases.
About the authors
Olagoke Olatunde
Fujian Institute of Research on the Structure of Matte, Chinese Academy of Sciences
Email: info@benthamscience.net
Jianping Yong
Xiamen Institute of Rare-earth Materials, Chinese Academy of Sciences
Author for correspondence.
Email: info@benthamscience.net
Canzhong Lu
Fujian Institute of Research on the Structure of Matter,, Chinese Academy of Sciences
Author for correspondence.
Email: info@benthamscience.net
Yanlin Ming
, Fujian Institute of Subtropical Botany
Email: info@benthamscience.net
References
- Li, T.K.; Liu, L.F. Tumor cell death induced by topoisomerase-targeting drugs. Annu. Rev. Pharmacol. Toxicol., 2001, 41(1), 53-77. doi: 10.1146/annurev.pharmtox.41.1.53 PMID: 11264450
- Pommier, Y. Topoisomerase I inhibitors: Camptothecins and beyond. Nat. Rev. Cancer, 2006, 6(10), 789-802. doi: 10.1038/nrc1977 PMID: 16990856
- McClendon, A.K.; Osheroff, N. DNA topoisomerase II, genotoxicity, and cancer. Mutat. Res., 2007, 623(1-2), 83-97. doi: 10.1016/j.mrfmmm.2007.06.009 PMID: 17681352
- Nitiss, J.L. Targeting DNA topoisomerase II in cancer chemotherapy. Nat. Rev. Cancer, 2009, 9(5), 338-350. doi: 10.1038/nrc2607 PMID: 19377506
- Nitiss, J.L. DNA topoisomerase II and its growing repertoire of biological functions. Nat. Rev. Cancer, 2009, 9(5), 327-337. doi: 10.1038/nrc2608 PMID: 19377505
- Schoeffler, A.J.; Berger, J.M. DNA topoisomerases: Harnessing and constraining energy to govern chromosome topology. Q. Rev. Biophys., 2008, 41(1), 41-101. doi: 10.1017/S003358350800468X PMID: 18755053
- Drake, F.H.; Zimmerman, J.P.; McCabe, F.L.; Bartus, H.F.; Per, S.R.; Sullivan, D.M.; Ross, W.E.; Mattern, M.R.; Johnson, R.K.; Crooke, S.T. Purification of topoisomerase II from amsacrine-resistant P388 leukemia cells. Evidence for two forms of the enzyme. J. Biol. Chem., 1987, 262(34), 16739-16747. doi: 10.1016/S0021-9258(18)49317-9 PMID: 2824504
- Drake, F.H.; Hofmann, G.A.; Bartus, H.F.; Mattern, M.R.; Crooke, S.T.; Mirabelli, C.K. Biochemical and pharmacological properties of p170 and p180 forms of topoisomerase II. Biochemistry, 1989, 28(20), 8154-8160. doi: 10.1021/bi00446a029 PMID: 2557897
- Vicker, N.; Burgess, L.; Chuckowree, I.S.; Dodd, R.; Folkes, A.J.; Hardick, D.J.; Hancox, T.C.; Miller, W.; Milton, J.; Sohal, S.; Wang, S.; Wren, S.P.; Charlton, P.A.; Dangerfield, W.; Liddle, C.; Mistry, P.; Stewart, A.J.; Denny, W.A. Novel angular benzophenazines: Dual topoisomerase I and topoisomerase II inhibitors as potential anticancer agents. J. Med. Chem., 2002, 45(3), 721-739. doi: 10.1021/jm010329a PMID: 11806724
- Arepalli, S.K.; Lee, C.; Sim, S.; Lee, K.; Jo, H.; Jun, K.Y.; Kwon, Y.; Kang, J.S.; Jung, J.K.; Lee, H. Development of 13H-benzofchromeno4,3-b1,7naphthyridines and their salts as potent cytotoxic agents and topoisomerase I/IIα inhibitors. Bioorg. Med. Chem., 2018, 26(18), 5181-5193. doi: 10.1016/j.bmc.2018.09.019 PMID: 30253887
- Khadka, D.B.; Cho, W.J. Topoisomerase inhibitors as anticancer agents: A patent update. Expert Opin. Ther. Pat., 2013, 23(8), 1033-1056. doi: 10.1517/13543776.2013.790958 PMID: 23611704
- Tan, K.B.; Dorman, T.E.; Falls, K.M.; Chung, T.D.; Mirabelli, C.K.; Crooke, S.T.; Mao, J. Topoisomerase II α and topoisomerase II β genes: Characterization and mapping to human chromosomes 17 and 3, respectively. Cancer Res., 1992, 52(1), 231-234. PMID: 1309226
- Vos, S.M.; Tretter, E.M.; Schmidt, B.H.; Berger, J.M. All tangled up: How cells direct, manage and exploit topoisomerase function. Nat. Rev. Mol. Cell Biol., 2011, 12(12), 827-841. doi: 10.1038/nrm3228 PMID: 22108601
- Woessner, R.D.; Mattern, M.R.; Mirabelli, C.K.; Johnson, R.K.; Drake, F.H. Proliferation- and cell cycle-dependent differences in expression of the 170 kilodalton and 180 kilodalton forms of topoisomerase II in NIH-3T3 cells. Cell Growth Differ., 1991, 2(4), 209-214. PMID: 1651102
- Velez-Cruz, R.; Osheroff, N. DNA topoisomerases: Type II. In: Encyclopedia of Biological Chemistry; Elsevier: San Diego, United States, 2004; pp. 806-811. doi: 10.1016/B0-12-443710-9/00680-3
- Lisby, M.; Olesen, J.R.; Skouboe, C.; Krogh, B.O.; Straub, T.; Boege, F.; Velmurugan, S.; Martensen, P.M.; Andersen, A.H.; Jayaram, M.; Westergaard, O.; Knudsen, B.R. Residues within the N-terminal domain of human topoisomerase I play a direct role in relaxation. J. Biol. Chem., 2001, 276(23), 20220-20227. doi: 10.1074/jbc.M010991200 PMID: 11283003
- Kim, K.H.; Kanbe, T.; Akashi, T.; Mizuguchi, I.; Kikuchi, A. Identification of a single nuclear localization signal in the C-terminal domain of an Aspergillus DNA topoisomerase II. Mol. Genet. Genomics, 2002, 268(3), 287-297. doi: 10.1007/s00438-002-0758-2 PMID: 12436251
- Berger, J.M.; Gamblin, S.J.; Harrison, S.C.; Wang, J.C. Structure and mechanism of DNA topoisomerase II. Nature, 1996, 379(6562), 225-232. doi: 10.1038/379225a0 PMID: 8538787
- Dutta, R.; Inouye, M. GHKL, an emergent ATPase/kinase superfamily. Trends Biochem. Sci., 2000, 25(1), 24-28. doi: 10.1016/S0968-0004(99)01503-0 PMID: 10637609
- Lindsey, R.H., Jr; Pendleton, M.; Ashley, R.E.; Mercer, S.L.; Deweese, J.E.; Osheroff, N. Catalytic core of human topoisomerase IIα: Insights into enzyme-DNA interactions and drug mechanism. Biochemistry, 2014, 53(41), 6595-6602. doi: 10.1021/bi5010816 PMID: 25280269
- Lee, S.; Jung, S.R.; Heo, K.; Byl, J.A.W.; Deweese, J.E.; Osheroff, N.; Hohng, S. DNA cleavage and opening reactions of human topoisomerase IIα are regulated via Mg2+ -mediated dynamic bending of gate-DNA. Proc. Natl. Acad. Sci. USA, 2012, 109(8), 2925-2930. doi: 10.1073/pnas.1115704109 PMID: 22323612
- Chen, S.F.; Huang, N.L.; Lin, J.H.; Wu, C.C.; Wang, Y.R.; Yu, Y.J.; Gilson, M.K.; Chan, N.L. Structural insights into the gating of DNA passage by the topoisomerase II DNA-gate. Nat. Commun., 2018, 9(1), 3085. doi: 10.1038/s41467-018-05406-y PMID: 30082834
- Dong, K.C.; Berger, J.M. Structural basis for gate-DNA recognition and bending by type IIA topoisomerases. Nature, 2007, 450(7173), 1201-1205. doi: 10.1038/nature06396 PMID: 18097402
- Leroy, D.; Alghist, G.C.; Roberts, E.; Filhol-Cochet, O.; Gasser, S.M. Mutations in the C-terminal domain of topoisomerase II affect meiotic function and interaction with the casein kinase 2 beta subunit. Mol. Cell. Biochem., 1999, 191(1/2), 85-95. doi: 10.1023/A:1006858210835 PMID: 10094396
- Cowell, I.G.; Willmore, E.; Chalton, D.; Marsh, K.L.; Jazrawi, E.; Fisher, L.M.; Austin, C.A. Nuclear distribution of human DNA topoisomerase IIbeta: A nuclear targeting signal resides in the 116-residue C-terminal tail. Exp. Cell Res., 1998, 243(2), 232-240. doi: 10.1006/excr.1998.4150 PMID: 9743583
- Champoux, J.J. DNA topoisomerases: Structure, function, and mechanism. Annu. Rev. Biochem., 2001, 70(1), 369-413. doi: 10.1146/annurev.biochem.70.1.369 PMID: 11395412
- Wang, J.C. Cellular roles of DNA topoisomerases: A molecular perspective. Nat. Rev. Mol. Cell Biol., 2002, 3(6), 430-440. doi: 10.1038/nrm831 PMID: 12042765
- Hsiang, Y.H.; Hertzberg, R.; Hecht, S.; Liu, L.F. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J. Biol. Chem., 1985, 260(27), 14873-14878. doi: 10.1016/S0021-9258(17)38654-4 PMID: 2997227
- Nitiss, J.; Wang, J.C. DNA topoisomerase-targeting antitumor drugs can be studied in yeast. Proc. Natl. Acad. Sci. USA, 1988, 85(20), 7501-7505. doi: 10.1073/pnas.85.20.7501 PMID: 2845409
- Lee, M.P.; Brown, S.D.; Chen, A.; Hsieh, T.S. DNA topoisomerase I is essential in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA, 1993, 90(14), 6656-6660. doi: 10.1073/pnas.90.14.6656 PMID: 8393572
- Kretzschmar, M.; Meisterernst, M.; Roeder, R.G. Identification of human DNA topoisomerase I as a cofactor for activator-dependent transcription by RNA polymerase II. Proc. Natl. Acad. Sci. USA, 1993, 90(24), 11508-11512. doi: 10.1073/pnas.90.24.11508 PMID: 8265582
- Mialon, A.; Sankinen, M.; Söderström, H.; Junttila, T.T.; Holmström, T.; Koivusalo, R.; Papageorgiou, A.C.; Johnson, R.S.; Hietanen, S.; Elenius, K.; Westermarck, J. DNA topoisomerase I is a cofactor for c-Jun in the regulation of epidermal growth factor receptor expression and cancer cell proliferation. Mol. Cell. Biol., 2005, 25(12), 5040-5051. doi: 10.1128/MCB.25.12.5040-5051.2005 PMID: 15923621
- Soret, J.; Gabut, M.; Dupon, C.; Kohlhagen, G.; Stévenin, J.; Pommier, Y.; Tazi, J. Altered serine/arginine-rich protein phosphorylation and exonic enhancer-dependent splicing in Mammalian cells lacking topoisomerase I. Cancer Res., 2003, 63(23), 8203-8211. PMID: 14678976
- Fortune, J.M.; Osheroff, N. Topoisomerase II as a target for anticancer drugs: When enzymes stop being nice. Prog. Nucleic Acid Res. Mol. Biol., 2000, 64, 221-253. doi: 10.1016/S0079-6603(00)64006-0 PMID: 10697411
- Radaeva, M.; Dong, X.; Cherkasov, A. The use of methods of computer-aided drug discovery in the development of topoisomerase II inhibitors: Applications and future directions. J. Chem. Inf. Model., 2020, 60(8), 3703-3721. doi: 10.1021/acs.jcim.0c00325 PMID: 32687346
- Ketron, A.C.; Osheroff, N. Phytochemicals as anticancer and chemopreventive topoisomerase II poisons. Phytochem. Rev., 2014, 13(1), 19-35. doi: 10.1007/s11101-013-9291-7 PMID: 24678287
- Deweese, J.E.; Osheroff, N. The DNA cleavage reaction of topoisomerase II: Wolf in sheeps clothing. Nucleic Acids Res., 2009, 37(3), 738-748. doi: 10.1093/nar/gkn937 PMID: 19042970
- Yang, X.; Li, W.; Prescott, E.D.; Burden, S.J.; Wang, J.C. DNA topoisomerase IIbeta and neural development. Science, 2000, 287(5450), 131-134. doi: 10.1126/science.287.5450.131 PMID: 10615047
- Linka, R.M.; Porter, A.C.G.; Volkov, A.; Mielke, C.; Boege, F.; Christensen, M.O. C-Terminal regions of topoisomerase II and II determine isoform-specific functioning of the enzymes in vivo. Nucleic Acids Res., 2007, 35(11), 3810-3822. doi: 10.1093/nar/gkm102 PMID: 17526531
- Haince, J.F.; Rouleau, M.; Poirier, G.G. Transcription. Gene expression needs a break to unwind before carrying on. Science, 2006, 312(5781), 1752-1753. doi: 10.1126/science.1129808 PMID: 16794066
- Ju, B.G.; Lunyak, V.V.; Perissi, V.; Garcia-Bassets, I.; Rose, D.W.; Glass, C.K.; Rosenfeld, M.G. A topoisomerase IIbeta-mediated dsDNA break required for regulated transcription. Science, 2006, 312(5781), 1798-1802. doi: 10.1126/science.1127196 PMID: 16794079
- Bailly, C. Contemporary challenges in the design of topoisomerase II inhibitors for cancer chemotherapy. Chem. Rev., 2012, 112(7), 3611-3640. doi: 10.1021/cr200325f PMID: 22397403
- Pommier, Y. Drugging topoisomerases: Lessons and challenges. ACS Chem. Biol., 2013, 8(1), 82-95. doi: 10.1021/cb300648v PMID: 23259582
- Pommier, Y.; Leo, E.; Zhang, H.; Marchand, C. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem. Biol., 2010, 17(5), 421-433. doi: 10.1016/j.chembiol.2010.04.012 PMID: 20534341
- Chen, W.; Qiu, J.; Shen, Y.M. Topoisomerase IIα, rather than IIβ, is a promising target in development of anti- cancer drugs. Drug Discov. Ther., 2012, 6(5), 230-237. doi: 10.5582/ddt.2012.v6.5.230 PMID: 23229142
- Fortune, J.M.; Osheroff, N. Merbarone inhibits the catalytic activity of human topoisomerase IIalpha by blocking DNA cleavage. J. Biol. Chem., 1998, 273(28), 17643-17650. doi: 10.1074/jbc.273.28.17643 PMID: 9651360
- Ohno, R.; Okada, K.; Masaoka, T.; Kuramoto, A.; Arima, T.; Yoshida, Y.; Ariyoshi, H.; Ichimaru, M.; Sakai, Y.; Oguro, M. An early phase II study of CPT-11: A new derivative of camptothecin, for the treatment of leukemia and lymphoma. J. Clin. Oncol., 1990, 8(11), 1907-1912. doi: 10.1200/JCO.1990.8.11.1907 PMID: 2230878
- Houghton, P.J.; Cheshire, P.J.; Myers, L.; Stewart, C.F.; Synold, T.W.; Houghton, J.A. Evaluation of 9-dimethylaminomethyl-10-hydroxycamptothecin against xenografts derived from adult and childhood solid tumors. Cancer Chemother. Pharmacol., 1992, 31(3), 229-239. doi: 10.1007/BF00685553 PMID: 1464161
- Johnson, R.K. SK&F 10864, Water soluble analogs of camptothecin with broad-spectrum activity in preclinical tumor models. Proc. Am. Assoc. Cancer Res., 1989, 30, 623.
- OConnor, P.M.; Kerrigan, D.; Bertrand, R.; Kohn, K.W.; Pommier, Y. 10,11-Methylenedioxycamptothecin, a topoisomerase I inhibitor of increased potency: DNA damage and correlation to cytotoxicity in human colon carcinoma (HT-29) cells. Cancer Commun., 1990, 2(12), 395-400. doi: 10.3727/095535490820873912 PMID: 2176090
- Young, R.C.; Ozols, R.F.; Myers, C.E. The anthracycline antineoplastic drugs. N. Engl. J. Med., 1981, 305(3), 139-153. doi: 10.1056/NEJM198107163050305 PMID: 7017406
- DArpa, P.; Liu, L.F. Topoisomerase-targeting antitumor drugs. Biochim. Biophys. Acta, 1989, 989(2), 163-177. PMID: 2557085
- David Foglesong, P.; Reckord, C.; Swink, S. Doxorubicin inhibits human DNA topoisomerase I. Cancer Chemother. Pharmacol., 1992, 30(2), 123-125. doi: 10.1007/BF00686403 PMID: 1318169
- Buzdar, A.U.; Marcus, C.; Blumenschein, G.R.; Smith, T.L. Early and delayed clinical cardiotoxicity of doxorubicin. Cancer, 1985, 55(12), 2761-2765. doi: 10.1002/1097-0142(19850615)55:123.0.CO;2-P PMID: 3922612
- Lee, J. H.; Ahn, B. Z. cytotoxic activity against L1210 cells of some raw drugs from the oriental medicine and folklore. Korean J. Pharmacogn., 1986, 17(4), 286-291.
- Kim, H.; Ahn, B.Z. Antitumor effects of acetylshikonin and some synthesized naphtharazin on L1210 and S-180 systems. Yakhak Hoeji, 1990, 34(4), 262-266.
- Murdock, K.C.; Child, R.G.; Fabio, P.F.; Angier, R.D.; Wallace, R.E.; Durr, F.E.; Citarella, R.V. Antitumor agents. 1. 1,4-Bis(aminoalkyl)amino-9,10-anthracenediones. J. Med. Chem., 1979, 22(9), 1024-1030. doi: 10.1021/jm00195a002 PMID: 490545
- Bodley, A.; Liu, L.F.; Israel, M.; Seshadri, R.; Koseki, Y.; Giuliani, F.C.; Kirschenbaum, S.; Silber, R.; Potmesil, M. DNA topoisomerase II-mediated interaction of doxorubicin and daunorubicin congeners with DNA. Cancer Res., 1989, 49(21), 5969-5978. PMID: 2551497
- Ahn, B.Z.; Baik, K.U.; Kweon, G.R.; Lim, K.; Hwang, B.D. Acylshikonin analogues: Synthesis and inhibition of DNA topoisomerase-I. J. Med. Chem., 1995, 38(6), 1044-1047. doi: 10.1021/jm00006a025 PMID: 7699697
- Evison, B.J.; Sleebs, B.E.; Watson, K.G.; Phillips, D.R.; Cutts, S.M. Mitoxantrone, more than just another topoisomerase II poison. Med. Res. Rev., 2016, 36(2), 248-299. doi: 10.1002/med.21364 PMID: 26286294
- De Isabella, P.; Capranico, G.; Palumbo, M.; Sissi, C.; Krapcho, A.P.; Zunino, F. Sequence selectivity of topoisomerase II DNA cleavage stimulated by mitoxantrone derivatives: Relationships to drug DNA binding and cellular effects. Mol. Pharmacol., 1993, 43(5), 715-721. PMID: 8388987
- Capranico, G.; Binaschi, M.; Borgnetto, M.E.; Zunino, F.; Palumbo, M. A protein-mediated mechanism for the DNA sequence-specific action of topoisomerase II poisons. Trends Pharmacol. Sci., 1997, 18(9), 323-329. doi: 10.1016/S0165-6147(97)01095-X PMID: 9345851
- Capranico, G.; De Isabella, P.; Tinelli, S.; Bigioni, M.; Zunino, F. Similar sequence specificity of mitoxantrone and VM-26 stimulation of in vitro DNA cleavage by mammalian DNA topoisomerase II. Biochemistry, 1993, 32(12), 3038-3046. doi: 10.1021/bi00063a015 PMID: 8384486
- Wu, C.C.; Li, Y.C.; Wang, Y.R.; Li, T.K.; Chan, N.L. On the structural basis and design guidelines for type II topoisomerase-targeting anticancer drugs. Nucleic Acids Res., 2013, 41(22), 10630-10640. doi: 10.1093/nar/gkt828 PMID: 24038465
- Crespi, M.D.; Ivanier, S.E.; Genovese, J.; Baldi, A. Mitoxantrone affects topoisomerase activities in human breast cancer cells. Biochem. Biophys. Res. Commun., 1986, 136(2), 521-528. doi: 10.1016/0006-291X(86)90471-7 PMID: 3010982
- Bhalla, K.; Ibrado, A.M.; Tourkina, E.; Tang, C.; Grant, S.; Bullock, G.; Huang, Y.; Ponnathpur, V.; Mahoney, M.E. High-dose mitoxantrone induces programmed cell death or apoptosis in human myeloid leukemia cells. Blood, 1993, 82(10), 3133-3140. doi: 10.1182/blood.V82.10.3133.3133 PMID: 8219202
- Bellosillo, B.; Colomer, D.; Pons, G.; Gil, J. Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells. Br. J. Haematol., 1998, 100(1), 142-146. doi: 10.1046/j.1365-2141.1998.00520.x PMID: 9450803
- Zhang, S.; Liu, X.; Bawa-Khalfe, T.; Lu, L.S.; Lyu, Y.L.; Liu, L.F.; Yeh, E.T.H. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat. Med., 2012, 18(11), 1639-1642. doi: 10.1038/nm.2919 PMID: 23104132
- Achmatowicz, O.; Szechner, B. Synthesis of enantiomerically pure anthracyclinones. Top. Curr. Chem., 2007, 282, 143-186. doi: 10.1007/128_2007_146
- Gottesman, M.M. How cancer cells evade chemotherapy: Sixteenth Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res., 1993, 53(4), 747-754. PMID: 8094031
- Kaye, S.B. The multidrug resistance phenotype. Br. J. Cancer, 1988, 58(6), 691-694. doi: 10.1038/bjc.1988.291 PMID: 3066393
- Aligiannis, N.; Pouli, N.; Marakos, P.; Skaltsounis, A.L.; Florent, J.C.; Perchellet, E.M.; Sperfslage, B.J.; McILVAIN, C.J.; Perchellet, J.P. Preparation and cytotoxic activity of some new rhodomycin derivatives bearing modifications in the sugar moiety. J. Antibiot. (Tokyo), 2002, 55(2), 181-190. doi: 10.7164/antibiotics.55.181 PMID: 12003000
- Sut, S.; Pavela, R.; Kolarčik, V.; Cappellacci, L.; Petrelli, R.; Maggi, F.; DallAcqua, S.; Benelli, G. Identification of onosma visianii roots extract and purified shikonin derivatives as potential acaricidal agents against tetranychus urticae. Molecules, 2017, 22(6), 1002. doi: 10.3390/molecules22061002 PMID: 28621748
- Majima, R.; Kuroda, C. On the colouring matter of lithospermum erythrorhizon. Acta Phytochim. (Tokyo), 1922, 1, 43-65.
- Brockmann, H. Die Konstitution des alkannins, shikonins and alkannans. Justus Liebigs Ann. Chem., 1936, 521(1), 1-47. doi: 10.1002/jlac.19365210102
- Papageorgiou, V.P.; Assimopoulou, A.N.; Couladouros, E.A.; Hepworth, D.; Nicolaou, K.C. The chemistry and biology of alkannin, shikonin, and related naphthazarin natural products. Angew. Chem. Int. Ed., 1999, 38(3), 270-301. doi: 10.1002/(SICI)1521-3773(19990201)38:33.0.CO;2-0 PMID: 29711637
- Yang, F.; Chen, Y.; Duan, W.; Zhang, C.; Zhu, H.; Ding, J. SH-7, a new synthesized shikonin derivative, exerting its potent antitumor activities as a topoisomerase inhibitor. Int. J. Cancer, 2006, 119(5), 1184-1193. doi: 10.1002/ijc.21943 PMID: 16570288
- Yoshida, L.S.; Kawada, T.; Irie, K.; Yuda, Y.; Himi, T.; Ikemoto, F.; Takano-Ohmuro, H. Shikonin directly inhibits nitric oxide synthases: Possible targets that affect thoracic aorta relaxation response and nitric oxide release from RAW 264.7 macrophages. J. Pharmacol. Sci., 2010, 112(3), 343-351. doi: 10.1254/jphs.09340FP PMID: 20197636
- Liang, W.; Cai, A.; Chen, G.; Xi, H.; Wu, X.; Cui, J.; Zhang, K.; Zhao, X.; Yu, J.; Wei, B.; Chen, L. Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen species. Sci. Rep., 2016, 6(1), 38267-38278. doi: 10.1038/srep38267 PMID: 27905569
- Mao, X.; Rong Yu, C.; Hua Li, W.; Xin Li, W. Induction of apoptosis by shikonin through a ROS/JNK-mediated process in Bcr/Abl-positive chronic myelogenous leukemia (CML) cells. Cell Res., 2008, 18(8), 879-888. doi: 10.1038/cr.2008.86 PMID: 18663379
- Baloch, S.K.; Ling, L.J.; Qiu, H.Y.; Ma, L.; Lin, H.Y.; Huang, S.C.; Qi, J.L.; Wang, X.M.; Lu, G.H.; Yang, Y.H. Synthesis and biological evaluation of novel shikonin ester derivatives as potential anti-cancer agents. RSC Adv., 2014, 4(67), 35588-35596. doi: 10.1039/C4RA05610H
- Kim, S.H.; Kang, I.C.; Yoon, T.J.; Park, Y.M.; Kang, K.S.; Song, G.Y.; Ahn, B.Z. Antitumor activities of a newly synthesized shikonin derivative, 2-hyim-DMNQ-S-33. Cancer Lett., 2001, 172(2), 171-175. doi: 10.1016/S0304-3835(01)00665-6 PMID: 11566493
- Lu, Q.; Liu, W.; Ding, J.; Cai, J.; Duan, W. Shikonin derivatives: Synthesis and inhibition of human telomerase. Bioorg. Med. Chem. Lett., 2002, 12(10), 1375-1378. doi: 10.1016/S0960-894X(02)00158-0 PMID: 11992780
- Hashimoto, S.; Xu, Y.; Masuda, Y.; Aiuchi, T.; Nakajo, S.; Uehara, Y.; Shibuya, M.; Yamori, T.; Nakaya, K. β-hydroxyisovalerylshikonin is a novel and potent inhibitor of protein tyrosine kinases. Jpn. J. Cancer Res., 2002, 93(8), 944-951. doi: 10.1111/j.1349-7006.2002.tb01341.x PMID: 12716473
- Wang, W.; Dai, M.; Zhu, C.; Zhang, J.; Lin, L.; Ding, J.; Duan, W. Synthesis and biological activity of novel shikonin analogues. Bioorg. Med. Chem. Lett., 2009, 19(3), 735-737. doi: 10.1016/j.bmcl.2008.12.032 PMID: 19111464
- Su, Y.; Xie, J.; Wang, Y.; Hu, X.; Lin, X. Synthesis and antitumor activity of new shikonin glycosides. Eur. J. Med. Chem., 2010, 45(7), 2713-2718. doi: 10.1016/j.ejmech.2010.02.002 PMID: 20403646
- Zhou, W.; Peng, Y.; Li, S.S. Semi-synthesis and anti-tumor activity of 5,8-O-dimethyl acylshikonin derivatives. Eur. J. Med. Chem., 2010, 45(12), 6005-6011. doi: 10.1016/j.ejmech.2010.09.068 PMID: 20970893
- Zhou, W.; Zhang, X.; Xiao, L.; Ding, J.; Liu, Q.H.; Li, S.S. Semi-synthesis and antitumor activity of 6-isomers of 5, 8-O-dimethyl acylshikonin derivatives. Eur. J. Med. Chem., 2011, 46(8), 3420-3427. doi: 10.1016/j.ejmech.2011.05.006 PMID: 21620530
- Wu, Y.; Wan, L.; Zheng, X.; Shao, Z.; Chen, J.; Chen, X.; Liu, L.; Kuang, W.; Tan, X.; Zhou, L. Inhibitory effects of β,β-dimethylacrylshikonin on hepatocellular carcinoma in vitro and in vivo. Phytother. Res., 2012, 26(5), 764-771. doi: 10.1002/ptr.3623 PMID: 22109831
- Shen, X.J.; Wang, H.B.; Ma, X.Q.; Chen, J.H. β,β-Dimethylacrylshikonin induces mitochondria dependent apoptosis through ERK pathway in human gastric cancer SGC-7901 cells. PLoS One, 2012, 7(7), e41773. doi: 10.1371/journal.pone.0041773 PMID: 22848597
- Rao, Z.; Liu, X.; Zhou, W.; Yi, J.; Li, S.S. Synthesis and antitumour activity of β-hydroxyisovalerylshikonin analogues. Eur. J. Med. Chem., 2011, 46(9), 3934-3941. doi: 10.1016/j.ejmech.2011.05.065 PMID: 21689869
- He, H.; Bai, L.P.; Jiang, Z.H. Synthesis and human telomeric G-quadruplex DNA-binding activity of glucosaminosides of shikonin/alkannin. Bioorg. Med. Chem. Lett., 2012, 22(4), 1582-1586. doi: 10.1016/j.bmcl.2011.12.143 PMID: 22281188
- Kretschmer, N.; Rinner, B.; Deutsch, A.J.A.; Lohberger, B.; Knausz, H.; Kunert, O.; Blunder, M.; Boechzelt, H.; Schaider, H.; Bauer, R. Naphthoquinones from Onosma paniculata induce cell-cycle arrest and apoptosis in melanoma Cells. J. Nat. Prod., 2012, 75(5), 865-869. doi: 10.1021/np2006499 PMID: 22530779
- Lin, H.Y.; Chen, W.; Shi, J.; Kong, W.Y.; Qi, J.L.; Wang, X.M.; Yang, Y.H. Design, synthesis and biological evaluation of cinnamic acyl shikonin derivatives. Chem. Biol. Drug Des., 2013, 81(2), 275-283. doi: 10.1111/cbdd.12077 PMID: 23066914
- Wang, X.M.; Lin, H.Y.; Kong, W.Y.; Guo, J.; Shi, J.; Huang, S.C.; Qi, J.L.; Yang, R.W.; Gu, H.W.; Yang, Y.H. Synthesis and biological evaluation of heterocyclic carboxylic acyl shikonin derivatives. Chem. Biol. Drug Des., 2014, 83(3), 334-343. doi: 10.1111/cbdd.12247 PMID: 24118825
- Guo, J.; Chen, X.F.; Liu, J.; Lin, H.Y.; Han, H.W.; Liu, H.C.; Huang, S.C.; Shahla, B.K.; Kulek, A.; Qi, J.L.; Wang, X.M.; Ling, L.J.; Yang, Y.H. Novel shikonin derivatives targeting tubulin as anticancer agents. Chem. Biol. Drug Des., 2014, 84(5), 603-615. doi: 10.1111/cbdd.12353 PMID: 24797889
- Lin, H.Y.; Han, H.W.; Bai, L.F.; Qiu, H.Y.; Yin, D.Z.; Qi, J.L.; Wang, X.M.; Gu, H.W.; Yang, Y.H. Design, synthesis and biological evaluation of shikonin thio-glycoside derivatives: New anti-tubulin agents. RSC Adv., 2014, 4(91), 49796-49805. doi: 10.1039/C4RA08810G
- Baloch, S.K.; Ma, L.; Xu, G.H.; Bai, L.F.; Zhao, H.; Tang, C.Y.; Pang, Y.J.; Yang, R.W.; Wang, X.M.; Lu, G.H.; Yang, Y.H. A potent anticancer agent of shikonin derivative targeting tubulin. Chirality, 2015, 27(3), 274-280. doi: 10.1002/chir.22425 PMID: 25663187
- Lin, H.Y.; Li, Z.K.; Bai, L.F.; Baloch, S.K.; Wang, F.; Qiu, H.Y.; Wang, X.; Qi, J.L.; Yang, R.W.; Wang, X.M.; Yang, Y.H. Synthesis of aryl dihydrothiazol acyl shikonin ester derivatives as anticancer agents through microtubule stabilization. Biochem. Pharmacol., 2015, 96(2), 93-106. doi: 10.1016/j.bcp.2015.04.021 PMID: 25957661
- Durchschein, C.; Hufner, A.; Rinner, B.; Stallinger, A.; Deutsch, A.; Lohberger, B.; Bauer, R.; Kretschmer, N. Synthesis of novel shikonin derivatives and pharmacological effects of cyclopropylacetylshikonin on melanoma cells. Molecules, 2018, 23(11), 2820. doi: 10.3390/molecules23112820 PMID: 30380765
- Park, D.G.; Kim, D.J.; Woo, B.H.; Kim, H.J.; Choi, Y.W.; Park, H.R. Isobutyrylshikonin has a potentially stronger cytotoxic effect in oral cancer cells than its analogue shikonin in vitro. Arch. Oral Biol., 2020, 116, 104774. doi: 10.1016/j.archoralbio.2020.104774 PMID: 32470830
- Shao, Y.Y.; Yin, Y.; Lian, B.P.; Leng, J.F.; Xia, Y.Z.; Kong, L.Y. Synthesis and biological evaluation of novel shikonin-benzobfuran derivatives as tubulin polymerization inhibitors targeting the colchicine binding site. Eur. J. Med. Chem., 2020, 190, 112105. doi: 10.1016/j.ejmech.2020.112105 PMID: 32035399
- Ross, W.; Rowe, T.; Glisson, B.; Yalowich, J.; Liu, L. Role of topoisomerase II in mediating epipodophyllotoxin-induced DNA cleavage. Cancer Res., 1984, 44(12 Pt 1), 5857-5860. PMID: 6094001
- Atwell, G.J.; Rewcastle, G.W.; Baguley, B.C.; Denny, W.A. Potential antitumor agents. 50. In vivo solid-tumor activity of derivatives of N-2-(dimethylamino)ethylacridine-4-carboxamide. J. Med. Chem., 1987, 30(4), 664-669. doi: 10.1021/jm00387a014 PMID: 3560161
- Fortune, J.M.; Velea, L.; Graves, D.E.; Utsugi, T.; Yamada, Y.; Osheroff, N. DNA topoisomerases as targets for the anticancer drug TAS-103: DNA interactions and topoisomerase catalytic inhibition. Biochemistry, 1999, 38(47), 15580-15586. doi: 10.1021/bi991792g PMID: 10569942
- Lhoste, J.M.; Lavelle, F.; Bissery, M.C.; Bisagni, E.; Bisagni, E. Synthesis and antitumor activity of 1-(dialkylamino)alkylamino-4-methyl-5H-pyrido4,3-bbenzoe- and -benzog)indoles. A new class of antineoplastic agents. J. Med. Chem., 1990, 33(5), 1519-1528. doi: 10.1021/jm00167a037 PMID: 2329575
- Perrin, D.; van Hille, B.; Barret, J.M.; Kruczynski, A.; Etiévant, C.; Imbert, T.; Hill, B.T. F 11782, a novel epipodophylloid non-intercalating dual catalytic inhibitor of topoisomerases I and II with an original mechanism of action. Biochem. Pharmacol., 2000, 59(7), 807-819. doi: 10.1016/S0006-2952(99)00382-2 PMID: 10718339
- Adjei, A.A.; Charron, M.; Rowinsky, E.K.; Svingen, P.A.; Miller, J.; Reid, J.M.; Sebolt-Leopold, J.; Ames, M.M.; Kaufmann, S.H. Effect of pyrazoloacridine (NSC 366140) on DNA topoisomerases I and II. Clin. Cancer Res., 1998, 4(3), 683-691. PMID: 9533538
- Salerno, S.; Da Settimo, F.; Taliani, S.; Simorini, F.; La Motta, C.; Fornaciari, G.; Marini, A.M. Recent advances in the development of dual topoisomerase I and II inhibitors as anticancer drugs. Curr. Med. Chem., 2010, 17(35), 4270-4290. doi: 10.2174/092986710793361252 PMID: 20939813
- Denny, W.; Baguley, B. Dual topoisomerase I/II inhibitors in cancer therapy. Curr. Top. Med. Chem., 2003, 3(3), 339-353. doi: 10.2174/1568026033452555 PMID: 12570767
- Tseng, C.H.; Tzeng, C.C.; Yang, C.L.; Lu, P.J.; Chen, H.L.; Li, H.Y.; Chuang, Y.C.; Yang, C.N.; Chen, Y.L. Synthesis and antiproliferative evaluation of certain indeno1,2-cquinoline derivatives. Part 2. J. Med. Chem., 2010, 53(16), 6164-6179. doi: 10.1021/jm1005447 PMID: 20662543
- Karki, R.; Thapa, P.; Yoo, H.Y.; Kadayat, T.M.; Park, P.H.; Na, Y.; Lee, E.; Jeon, K.H.; Cho, W.J.; Choi, H.; Kwon, Y.; Lee, E.S. Dihydroxylated 2,4,6-triphenyl pyridines: Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structureactivity relationship study. Eur. J. Med. Chem., 2012, 49, 219-228. doi: 10.1016/j.ejmech.2012.01.015 PMID: 22318164
- Abdel-Aziz, M.; Park, S.E.; Abuo-Rahma, G.E.D.A.A.; Sayed, M.A.; Kwon, Y. Novel N-4-piperazinyl-ciprofloxacin-chalcone hybrids: Synthesis, physicochemical properties, anticancer and topoisomerase I and II inhibitory activity. Eur. J. Med. Chem., 2013, 69, 427-438. doi: 10.1016/j.ejmech.2013.08.040 PMID: 24090914
- Dalla Via, L.; Marzaro, G.; Ferrarese, A.; Gia, O.; Chilin, A. Pyrroloquinolinone-based dual topoisomerase I/II inhibitor. Eur. J. Med. Chem., 2014, 77, 103-109. doi: 10.1016/j.ejmech.2014.02.064 PMID: 24631729
- Yao, B.L.; Mai, Y.W.; Chen, S.B.; Xie, H.T.; Yao, P.F.; Ou, T.M.; Tan, J.H.; Wang, H.G.; Li, D.; Huang, S.L.; Gu, L.Q.; Huang, Z.S. Design, synthesis and biological evaluation of novel 7-alkylamino substituted benzoaphenazin derivatives as dual topoisomerase I/II inhibitors. Eur. J. Med. Chem., 2015, 92, 540-553. doi: 10.1016/j.ejmech.2015.01.024 PMID: 25599951
- Karki, R.; Jun, K.Y.; Kadayat, T.M.; Shin, S.; Thapa Magar, T.B.; Bist, G.; Shrestha, A.; Na, Y.; Kwon, Y.; Lee, E.S. A new series of 2-phenol-4-aryl-6-chlorophenyl pyridine derivatives as dual topoisomerase I/II inhibitors: Synthesis, biological evaluation and 3D-QSAR study. Eur. J. Med. Chem., 2016, 113, 228-245. doi: 10.1016/j.ejmech.2016.02.050 PMID: 26945111
- Fujii, N.; Yamashita, Y.; Arima, Y.; Nagashima, M.; Nakano, H. Induction of topoisomerase II-mediated DNA cleavage by the plant naphthoquinones plumbagin and shikonin. Antimicrob. Agents Chemother., 1992, 36(12), 2589-2594. doi: 10.1128/AAC.36.12.2589 PMID: 1336338
- Plyta, Z.F.; Li, T.; Papageorgiou, V.P.; Mellidis, A.S.; Assimopoulou, A.N.; Pitsinos, E.N.; Couladouros, E.A. Inhibition of topoisomerase I by naphthoquinone derivatives. Bioorg. Med. Chem. Lett., 1998, 8(23), 3385-3390. doi: 10.1016/S0960-894X(98)00600-3 PMID: 9873739
- Zhang, F.L.; Wang, P.; Liu, Y.H.; Liu, L.; Liu, X.B.; Li, Z.; Xue, Y.X. Topoisomerase I inhibitors, shikonin and topotecan, inhibit growth and induce apoptosis of glioma cells and glioma stem cells. PLoS One, 2013, 8(11), e81815. doi: 10.1371/journal.pone.0081815 PMID: 24303074
- Ogawa, Y.; Kawano, Y.; Yamazaki, Y.; Onishi, Y. Shikonin shortens the circadian period: Possible involvement of Top2 inhibition. Biochem. Biophys. Res. Commun., 2014, 443(1), 339-343. doi: 10.1016/j.bbrc.2013.11.116 PMID: 24321095
- Su, L.; Liu, L.; Wang, Y.; Yan, G.; Zhang, Y. Long-term systemic toxicity of shikonin derivatives in Wistar rats. Pharm. Biol., 2014, 52(4), 486-490. doi: 10.3109/13880209.2013.846913 PMID: 24192282
Supplementary files
