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Extending Natures Leads: The Anticancer Agent Ellipticine
Abstract
The natural plant product ellipticine was isolated in 1959 from the Australian evergreen tree of the Apocynaceae family. This compound was found to be an extremely promising anticancer drug. The planar polycyclic structure was found to interact with DNA through intercalation, exhibiting a high DNA binding affinity (10(6) M(-1)). The presence of protonatable ring nitrogens distinguished ellipticine from other simple intercalators. Both monocationic and uncharged species were found to be present under physiological conditions. The positive charge stabilized the binding of ellipticine to nucleic acids, while the more lipophilic uncharged compound was shown to readily penetrate membrane barriers. The structural nature of these compounds offers a plausible basis for the implication of multiple modes of action, including DNA binding, interactions with membrane barriers, oxidative bioactivation and modification of enzyme function; most notably that of topoisomerase II and telomerase. Pharmacologically, a number of toxic side effects have been shown to be problematic, but the amenability of ellipticine towards systematic structural modification has permitted the extensive application of rational drug design. A number of successful ellipticine analogs have been designed and synthesized with improved toxicities and anticancer activities. More recently the synthetic focus has broadened to include the design of hybrid compounds, as well as drug delivery conjugates. Considerable research efforts have been directed towards gaining a greater understanding of the mechanism of action of these drugs that will aid further in the optimization of drug design.
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“This outcome may be attributed to the inadequate pharmacokinetic parameters of ellipticine52”
From Impairing the interaction between Erg11 and cytochrome P450 reductase Ncp1 enhances azoles’ antifungal activities (2025) · cites this paper as [52]
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Items 101–137 of 137
Other Anticancer Drugs Targeting DNA and DNA-Associated Enzymes
Avendaño, C., & Menéndez, J. C. (2015) · Elsevier eBooks · doi:10.1016/b978-0-444-62649-3.00007-7 · Cited by 6
Meza‐Menchaca, T., Lizano-Soberón, M., Trigos, Á., et al. (2020) · Medicinal Chemistry · doi:10.2174/1573406416666200129145733 · Cited by 5
Saniova, B., Krkoska, D., Taziarova, M., et al. (2013) · PubMed · Cited by 4
Kato, A., Nagatsuka, Y., Hiratsuka, T., et al. (2016) · Tetrahedron · doi:10.1016/j.tet.2016.05.068 · Cited by 4
The synthesis of 7,8,9,10-tetrafluoroellipticine
Gruver, E. J., Onyango, E. O., & Gribble, G. W. (2018) · ARKIVOC · doi:10.24820/ark.5550190.p010.414 · Cited by 4
Therapeutic Utilization of Bioactive Compounds and Phytochemicals
Sharma, H. G., Bhat, A. H., & Chaubey, A. K. (2022) · Advances in medical diagnosis, treatment, and care (AMDTC) book series · doi:10.4018/978-1-6684-5129-8.ch001 · Cited by 3
Chemical-Biology of Natural Products from Medicinal Plants for Cancer Therapy
Efferth, T., & Wink, M. (2010) · Springer eBooks · doi:10.1007/978-1-4419-0020-3_22 · Cited by 3
“Protonable ring nitrogens can stabilize the alkaloid-DNA complex by binding to negatively charged DNA [48, 49 ].”
BackgroundMarepu, N., Gosi, M., Vedula, S. S., et al. (2019) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557518666180727170055 · Cited by 3
Prospects of Traditionally important Apocynaceae plants of India in Cancer Remediation
Devi, N., Gupta, A. K., & Prajapati, S. K. (2019) · Journal of Drug Delivery and Therapeutics · doi:10.22270/jddt.v9i1.2208 · Cited by 3
Mani, D. N., SHUKLA, S., & SHUKLA, Y. N. (2020) · Journal of Medicinal and Aromatic Plant Sciences · doi:10.62029/jmaps.v42i1.mani · Cited by 3
Disruptive DNA Intercalation Is the Mode of Interaction Behind Niacinamide Antimicrobial Activity
Rasis, M., Ziklo, N., & Salama, P. (2025) · Microorganisms · doi:10.3390/microorganisms13071636 · Cited by 2
“Induction of local “unzipping” of the DNA helix by Ellipticine, adriamycin, and AO was shown to reduce the Tm by approximately 5 ◦ C [17–19].”
Synthesis and cytotoxicity evaluation of olivacine-indole hybrids tethered by alkyl linkers
Diez, C., Céspedes, M. A., Venosa, G. M. D., et al. (2021) · Natural Product Research · doi:10.1080/14786419.2021.1880401 · Cited by 2
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Sankar, R., Vasuki, G., Kumar, S. Y., et al. (2024) · Chemical Physics Impact · doi:10.1016/j.chphi.2024.100530 · Cited by 2
Synthesis and Cytotoxicity of Novel Bis-Ellipticines and Bis-Isoellipticines
Gribble, G. W., & Obaza-Nutaitis, J. A. (2018) · Heterocycles · doi:10.3987/com-18-s(f)6 · Cited by 2
NEW 6H- INDOLO(2,3-B)QUINOLINE O-AMINOGLYCOSIDES OVERCOMING ANTICANCER MULTIDRUG RESISTANCE
Badowska-Rosłonek, K., Godlewska, J., Świtalska, M., et al. (2013) · Cited by 1
DNA intercalation and topoisomerase inhibition
Avendaño, C., & Menéndez, J. C. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-818549-0.00010-8 · Cited by 1
Mishra, A. P., Sharma, D., & Tiwari, S. N. (2023) · Springer Proceedings in Materials · doi:10.1007/978-981-99-4685-3_16 · Cited by 1
Reyes, J. A. A., Bahsas, H. B. A., Méndez, P. D., et al. (2006) · Avances en Química · Cited by 1
Zayas, B. (2015) · Journal of Cancer Research and Therapeutic Oncology · doi:10.17303/jcrto.2015.103
“Ellipticine has been studied since the 1959 and has shown a variety of biological activities such as DNA interaction, anti-cancer activity and mitochondrial uptake [11].”
Indole Derivatives as DNA Minor Groove Binders
Gupta, S. P., Pandya, P., Kumar, G. S., et al. (2011) · Springer eBooks · doi:10.1007/978-3-642-23394-4_32
Desforges, G., Picot, L., Montagne, C., et al. (2005) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756360500212621
Fung, S. (2008) · UWSpace (University of Waterloo)
Sassano, M. F. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/wwr3-7m34
Devi, N., Gupta, A. K., & Prajapati, S. K. (2019) · Journal of Drug Delivery and Therapeutics · doi:10.22270/jddt.v9i4-s.3906
“Apocynaceae family, the fifth valuable medicinal plant family among Angiosperms is also called as Dogbane or Arrow poisons family [12-20].”
BackgroundEffects of natural products on the activity of human topoisomerase II
Vann, K. R. (2016)
Gaté, L. (2007) · xPharm: The Comprehensive Pharmacology Reference · doi:10.1016/b978-008055232-3.61672-1
Denman, B., Kavaguti, D. M., & Roberts, C. C. (2025) · ChemRxiv · doi:10.26434/chemrxiv-2025-92njk
Santos, K. C. S., & de Sousa, R. L. (2025) · Matéria (Rio de Janeiro) · doi:10.1590/1517-7076-rmat-2025-0335
Nanoparticle-Catalyzed Green and Sustainable Synthesis of Carbazole Scaffolds (A Review)
Gautam, A., Sharma, S., Singh, P. P., Sharma, B., Gaur, D., Mishra, K., & Chaudhary, S. (2025) · Russian Journal of Organic Chemistry · doi:10.1134/s1070428025601244
Harnessing nanotechnology: ellipticine nanoformulations in the fight against cancer
Das, I., Kamath, V., Bhat, K. S., et al. (2026) · Cancer Nanotechnology · doi:10.1186/s12645-026-00365-2
Denman, B., Kavaguti, D. M., & Roberts, C. C. (2026) · ACS Catalysis · doi:10.1021/acscatal.6c01835
Uses of Ionic Liquids in the Synthesis of Carbazole and its Derivatives
Sharma, S., Sharma, B., Singh, P. P., et al. (2026) · Chemistry Africa · doi:10.1007/s42250-026-01684-y
Munawar, S., Malik, S. A., Kamal, S., Mansha, A., Zahoor, A. F., Khan, S. G., Malik, F. Z., & Said, M. A. (2026) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2026.147350
Metadata
- Authors
- Garbett, N., & Graves, D.
- Affiliations
- University of Alabama at Birmingham (US)
- Venue
- Current Medicinal Chemistry-Anti-Cancer Agents
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2004-03-01
- Volume
- 4
- Issue
- 2
- Pages
- 149-172
- ISSN
- 1568-0118 (ISSN-L)
- OpenAlex
- W2077301074
- Cited by
- 137
- References
- 0
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 3 · 2023: 2 · 2022: 8 · 2021: 2 · 2020: 5 · 2019: 10 · 2018: 7 · 2017: 4 · 2016: 9 · 2015: 11 · 2014: 7 · 2013: 9 · 2012: 9
- FWCI
- 1.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Anti-Cancer Agents in Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and bioactivity of alkaloids
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
- Keywords
- ellipticine, DNA intercalation, anticancer agents, Apocynaceae, topoisomerase II, telomerase, rational drug design, hybrid molecules, membrane permeability, drug toxicity, mechanism of action
- MeSH terms
- Animals, Antineoplastic Agents, Ellipticines, Humans, Phytotherapy, Neoplasms, Structure-Activity Relationship, Apocynaceae
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