(+)-Camptothecin
[CAS# 7689-03-4]

Identification

• Classification: API >> Antineoplastic agents >> Natural source antineoplastic agents
• Name: (+)-Camptothecin
• Synonyms: 4-Ethyl-4-hydroxy-1H-pyrano-[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione
• Molecular Formula: C₂₀H₁₆N₂O₄
• Molecular Weight: 348.36
• CAS Registry Number: 7689-03-4
• EC Number: 616-407-7
• SMILES: CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=CC5=CC=CC=C5N=C4C3=C2)O

Properties

• Density: 1.5±0.1 g/cm³ Calc.^*
• Melting point: 260 °C (Decomposes) (Expl.)
• Boiling point: 757.0±60.0 °C 760 mmHg (Calc.)^*
• Flash point: 411.6±32.9 °C (Calc.)^*
• Solubility: DMSO: 10 mM (Expl.)
• Index of refraction: 1.746 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS06;GHS08 Danger
• Risk Statements: H301-H340
• Safety Statements: P203-P264-P270-P280-P301+P316-P318-P321-P330-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	3	H301
Germ cell mutagenicity	Muta.	1B	H340
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Acute toxicity	Acute Tox.	4	H302
Specific target organ toxicity - single exposure	STOT SE	3	H335

• Transport Information: UN 1544

Discovery and Applications

(+)-Camptothecin is a naturally occurring pentacyclic quinoline alkaloid primarily isolated from the bark and stems of Camptotheca acuminata, commonly known as the “happy tree” native to China. Chemically, it features a unique pentacyclic structure with a lactone ring and a quinoline moiety, which is critical for its biological activity. (+)-Camptothecin has been extensively studied for its potent anticancer properties, particularly as a topoisomerase I inhibitor, making it a key molecule in oncology research and drug development.

The discovery of camptothecin dates back to the 1960s when researchers were exploring traditional Chinese medicinal plants for bioactive compounds. Isolation and structural characterization were accomplished using chromatographic techniques and spectroscopic methods such as nuclear magnetic resonance (NMR) and mass spectrometry, allowing researchers to identify its unique chemical structure and investigate its pharmacological activity.

Pharmacologically, (+)-camptothecin acts as a selective inhibitor of DNA topoisomerase I, an enzyme essential for DNA replication and transcription. By stabilizing the covalent complex between topoisomerase I and DNA, camptothecin prevents the re-ligation of single-stranded DNA breaks, ultimately leading to double-strand breaks during DNA replication and inducing apoptosis in rapidly dividing cancer cells. This mechanism underpins its potent antitumor activity against a broad spectrum of cancers, including colon, lung, breast, and ovarian cancers.

Despite its efficacy, the clinical use of (+)-camptothecin is limited by poor solubility and chemical instability, particularly the hydrolysis of the lactone ring under physiological conditions, which reduces its cytotoxic activity. To overcome these limitations, researchers have developed water-soluble derivatives such as irinotecan and topotecan, which maintain the pharmacological activity of camptothecin while improving bioavailability and clinical applicability. These derivatives are now widely used in chemotherapy regimens for various cancers.

In addition to its anticancer properties, (+)-camptothecin exhibits selective cytotoxicity toward proliferating cells while sparing non-dividing cells, which contributes to its therapeutic potential and guides dosing strategies in clinical use. Its activity has also spurred research into nanoparticle formulations, liposomal delivery systems, and conjugates with targeting ligands to enhance tumor specificity, reduce systemic toxicity, and improve pharmacokinetics.

The impact of (+)-camptothecin extends beyond direct clinical applications. Its discovery and mechanism of action have provided insights into DNA topology, enzyme function, and apoptosis pathways, informing the design of novel topoisomerase inhibitors and guiding cancer pharmacology research. The compound also serves as a scaffold for medicinal chemists to develop new analogs with improved potency, stability, and selectivity.

Overall, (+)-camptothecin is a bioactive alkaloid with a pentacyclic structure and a lactone moiety, primarily recognized for its role as a topoisomerase I inhibitor. Its discovery from Camptotheca acuminata and subsequent development of derivatives have revolutionized cancer chemotherapy, highlighting its significance in both pharmacology and oncology research.

References

1998. Increased Camptothecin Toxicity Induced in Mammalian Cells Expressing Saccharomyces cerevisiae DNA Topoisomerase I. The Journal of biological chemistry.
DOI: 10.1074/jbc.273.14.8425

1997. DNA-Topoisomerase I, a new target for the treatment of neuroblastoma. European journal of cancer (Oxford, England : 1990).
DOI: 10.1016/s0959-8049(97)00296-7

2024. Advancing alkaloid-based medicines: medical applications, scalable production and synthetic innovations. Phytochemistry Reviews.
DOI: 10.1007/s11101-024-10050-0