Cited by 137Synthesis and bioactivity of alkaloidsCancer therapeutics and mechanismsBioactive Compounds and Antitumor Agents

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Extending Natures Leads: The Anticancer Agent Ellipticine

Garbett, Nichola, Graves, David·2004·Current Medicinal Chemistry-Anti-Cancer Agents

DOI 10.2174/1568011043482070

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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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The anticancer agent ellipticine binds to glycosaminoglycans at mildly acidic pH characteristic of the extracellular matrix of tumor tissues
Zsila, F. (2015) · RSC Advances · doi:10.1039/c5ra23437a · Cited by 11
Impact of histone deacetylase inhibitor valproic acid on the anticancer effect of etoposide on neuroblastoma cells.
Groh, T., Hraběta, J., Poljaková, J., et al. (2012) · PubMed · Cited by 11
Impairing the interaction between Erg11 and cytochrome P450 reductase Ncp1 enhances azoles’ antifungal activities
Li, W., Whiteway, M., Hang, S., Yu, J., Lu, H., & Jiang, Y. (2025) · Nature Communications · doi:10.1038/s41467-025-62131-z · Cited by 13
“This outcome may be attributed to the inadequate pharmacokinetic parameters of ellipticine 52 , which likely hinder its ef ﬁ cacy in enhancing the antifungal action of FLC in this context.”
A steady-state and time-resolved fluorescence study on liposome-calf thymus DNA interaction: probed by an anticancer drug ellipticine
Das, A., Thakur, R., & Chakraborty, A. (2013) · RSC Advances · doi:10.1039/c3ra43037e · Cited by 10
Ellipticine induces apoptosis in T-cell lymphoma via oxidative DNA damage
Savorani, C., Manfé, V., Biskup, E., & Gniadecki, R. (2014) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.3109/10428194.2014.929673 · Cited by 10
Expression Levels of Enzymes Metabolizing an Anticancer Drug Ellipticine Determined by Electromigration Assays Influence its Cytotoxicity to Cancer Cells - A Comparative Study
Stiborová, M., Poljaková, J., Mrízová, I., Bořek-Dohalská, L., Eckschlager, T., Adam, V., Kizek, R., & Frei, E. (2014) · International Journal of Electrochemical Science · doi:10.1016/s1452-3981(23)08197-x · Cited by 10
Anticancer Tetrahydrocarbazoles: A Wide Journey from 2000 Till Date
Kumar, N., & Gupta, P. (2022) · Letters in Drug Design & Discovery · doi:10.2174/1570180820666221028163319 · Cited by 9
Synthesis and in vitro Antitumor Activity of 9-Hydroxyellipticine Derivatives with Glucose Conjugation via Triazolylmethyl Succinate Linker
Konakahara, T., Sato, N., Kawai, Y., Akaba, Y., Honma, S., & Sakai, N. (2016) · Heterocycles · doi:10.3987/com-16-13404 · Cited by 9
Recent synthesis of ellipticine and its derivatives
Ibrahim‐Ouali, M., & Dumur, F. (2018) · ARKIVOC · doi:10.24820/ark.5550190.p010.445 · Cited by 9
Co-delivery of drug nanoparticles and siRNA mediated by a modified cell penetrating peptide for inhibiting cancer cell proliferation
Chu, D., Xu, W., Ran, P., & Chen, P. (2015) · RSC Advances · doi:10.1039/c4ra14827d · Cited by 8
Fischer Reaction in the Synthesis of New Triterpene Indoles of the Fusidane Series
Salimova, E. V., & Parfenova, L. V. (2022) · Russian Journal of Organic Chemistry · doi:10.1134/s1070428022010031 · Cited by 8
Preparation of p H ‐ R esponsive Polymer Core– S hell Nanospheres for Delivery of Hydrophobic Antineoplastic Drug Ellipticine
Wang, H., Yang, L., & Rempel, G. L. (2013) · Macromolecular Bioscience · doi:10.1002/mabi.201300333 · Cited by 8
Advances in heterocycles as DNA intercalating cancer drugs
Das, A., & Banik, B. K. (2022) · Physical Sciences Reviews · doi:10.1515/psr-2021-0065 · Cited by 7
Formation of DNA Adducts by Ellipticine and Its Micellar Form in Rats — A Comparative Study
Stiborová, M., Manhartova, Z., Hodek, P., Adam, V., Kizek, R., & Frei, E. (2014) · Sensors · doi:10.3390/s141222982 · Cited by 7
“Ellipticine (5,11-dimethyl-6H-pyrido(4,3-b)carbazole) and its derivatives are efficient anticancer compounds that function through multiple mechanisms participating in cell cycle arrest and initiation of apoptosis (for a summary see [1–6]).”
Background
The Anticancer Drug Ellipticine Induces Cytochromes P450 1A1, 1A2 and 3A, Cytochrome b5 and NADPH:Cytochrome P450 Oxidoreductase in Rat Liver, Kidney and Lung
Vranová, I., Moserová, M., Hodek, P., et al. (2013) · International Journal of Electrochemical Science · doi:10.1016/s1452-3981(23)14249-0 · Cited by 7
Determination of binding modes and binding constants for the complexes of 6H-pyrido[4,3-b]carbazole derivatives with DNA
Shimazu, A., Kawagoshi, M., Takeda, S., et al. (2016) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2016.12.031 · Cited by 7
A study of the properties, reactivity and anticancer activity of novel N-methylated-3-thiazolyl or 3-thienyl carbazoles and their Pd(II) and Pt(II) complexes
Reig, M., Bosque, R., Font‐Bardía, M., et al. (2018) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2018.03.008 · Cited by 7
Molecular interactions of the anticancer agent ellipticine with glycosaminoglycans by in silico analysis
Zsila, F., & Samsonov, S. A. (2018) · Carbohydrate Research · doi:10.1016/j.carres.2018.03.014 · Cited by 7
Medicinal plants: nutritional, immunological and therapeutic role in treating cancer-related malnutrition: a comprehensive review
El‐Saadony, M. T., Alkafaas, S. S., Saad, A. M., et al. (2025) · Cancer Cell International · doi:10.1186/s12935-025-03720-2 · Cited by 6
Structural modification of ellipticine derivatives with alkyl groups of varying length is influential on their effects on human DNA topoisomerase II: a combined experimental and computational study
Kuskucu, M., Akyildiz, V., Kulmány, Á. E., et al. (2019) · Medicinal Chemistry Research · doi:10.1007/s00044-019-02472-9 · Cited by 6
Bioactive properties of native Australian medicinal plants.
Jones, G. L., Smith, J. E., Watson, K., Acharya, S. N., & Thomas, J. E. (2007) · EPubDev Repository · Cited by 6
Pharmacokinetics of Peptide Mediated Delivery of Anticancer Drug Ellipticine
Ma, W., Lu, S., Pan, P., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0043684 · Cited by 6
“It can inhibit osteolytic and breast cancer metastases, kidney cancer, brain tumor and acute myeloblastic leukemia [9–10].”
Background
An amphipathic lytic peptide for enhanced and selective delivery of ellipticine
Lu, S., Ding, Y., Wu, Y. F., et al. (2016) · Journal of Materials Chemistry B · doi:10.1039/c6tb00529b · Cited by 6
Dimeric binding of plant alkaloid ellipticine to human serum proteins
Zsila, F., & Beke‐Somfai, T. (2016) · RSC Advances · doi:10.1039/c6ra06078a · Cited by 6

Authors: Garbett, N., & Graves, D.
Affiliations: University of Alabama at Birmingham (US)
ORCID: Garbett, Nichola
Graves, David
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)
DOI: 10.2174/1568011043482070
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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Extending Natures Leads: The Anticancer Agent Ellipticine

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