Extending Natures Leads: The Anticancer Agent Ellipticine

Garbett, Nichola; Graves, David

doi:10.2174/1568011043482070

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

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 suboptimal murine efficacy of ellipticine may be attributed to inadequate pharmacokinetic parameters of ellipticine.
“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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Background
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Background
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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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