Synonym name:
Catalogue No.: BP0324
Cas No.: 2468-21-5
Formula: C₂₁H₂₄N₂O₂
Mol Weight: 336.435
Botanical Source: Alkaloid from Catharanthus ovalis and other Catharanthus spp. and from Vinca rosea (Apocynaceae)

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.

For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Catharanthine (CAS No.: 2468-21-5) is an important alkaloid isolated from the periwinkle (Catharanthus roseus) and is a member of the periwinkle alkaloid family. These alkaloids have attracted significant attention for their significant anticancer activity and multi-target pharmacological effects. Vincristine alkaloids, as one of the active components in the alkaloids of the periwinkle flower, have attracted extensive research in recent years in pharmacology and natural product drug development. It not only exhibits inhibitory effects on various tumor cells, especially its potential therapeutic value in hematologic malignancies such as leukemia, but also, due to its inhibitory effect on voltage-dependent L-type calcium channels (VOCC), shows potential for modulating cardiovascular function.

This paper aims to systematically review the chemical structure and physicochemical properties of vincrinit alkali, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics, and to explore its prospects and challenges in clinical application, providing theoretical basis and reference for subsequent basic research and drug development.

Chemical structure and physicochemical properties

The chemical name of vincrisin alkali is (+)-3,4-Didehydrocoronaridine, with the molecular formula C21H26N2O2 and a molecular weight of 336.43. Its structure belongs to the indole alkaloid class, featuring a complex polycyclic structure and multiple chiral centers. The LogP value of vincrisoline alkaloid is 3.1, indicating moderate lipid solubility, which facilitates cell membrane penetration and distribution in vivo. Its topological pole surface area (TPSA) is 55.12 Ų, and it has 4 hydrogen bond acceptors, indicating that it may form certain hydrogen bonds when binding with biological macromolecules.

The molecular structure of vincrist alkali contains indole rings and various functional groups, endowing it with rich chemical and biological reactivity. The structural stability and three-dimensional configuration form the basis for its biological activity. Notably, vincristine alkaloid has a high blood-brain barrier permeability (BBB), suggesting its potential application in central nervous system diseases.

Plant Origins and Extraction Methods

Vincristine mainly comes from the periwinth flower (Catharanthus roseus), a perennial herbaceous plant of the Oleaceae family, widely distributed in tropical and subtropical regions. Periwinkle contains various alkaloids, with vincristine being one of its important components. It often coexists with other vincristine alkaloids such as vincristine and vinblastine.

Traditional extraction methods mostly use organic solvent extraction combined with acid-base stepwise extraction. The general process includes:

1. Plant material pretreatment: Dry and crush periwinkle.
2. Organic solvent extraction methods: Methanol, ethanol, or ethyl acetate are commonly used for extraction to extract alkaloid mixtures.
3. Acid-base separation: Using acidic aqueous solutions to convert alkaloids into salt forms, separating impurities from the aqueous phase, and then using alkaline aqueous solutions to precipitate the alkaloid in its free state.
4. Column chromatography purification: Further purification of vincristine alkali using silica gel column chromatography or high-performance liquid chromatography (HPLC) technology.

In recent years, new technologies such as ultrasound-assisted extraction and microwave-assisted extraction have been applied to improve the extraction efficiency and purity of vinchun alkali. In addition, research on biosynthetic pathways also offers the possibility of increasing vincristine alkali yield through genetic engineering methods.

Pharmacological activity research

Anticancer activity

Vincristine, as an important component of avino alkaloids, demonstrates remarkable antitumor activity. Research shows that vincristine can inhibit tumor cell proliferation, induce apoptosis, and block the tumor cell cycle through multiple mechanisms. Especially in leukemia cell lines, vincristine exhibits strong cytotoxicity.

Its anticancer activity is closely related to the regulation of various signaling pathways, including key molecules such as AMPK, MCL1, BCL2, NOTCH1, and STAT3, which affect cell metabolism, apoptosis, and proliferation. Vincristine alkaloids can also affect targets such as TOP1 and SIRT1, regulating DNA repair and cellular stress responses.

Cardiovascular system function

Vincristine inhibits voltage-driven L-type calcium channels (VOCC), with an IC50 of 220 μM in cardiomyocytes and 8 μM in vascular smooth muscle cells (VSMC), demonstrating high selectivity and sensitivity to calcium channels in vascular smooth muscle cells. By inhibiting VOCC, vincristine lowers intracellular calcium ion concentration, causing vasodilation and thereby lowering blood pressure (BP) and heart rate (HR). This effect gives it potential value in treating hypertension and related cardiovascular diseases.

Other pharmacological effects

Current research shows that vincristine also has certain effects on the central nervous system, possibly regulating neuronal excitability and neuroprotection through its high blood-brain barrier permeability. In addition, the anti-inflammatory and antioxidant effects of vincristine alkali are gradually receiving attention, but the related mechanisms still require further exploration.

Mechanism of action and molecular targets

The pharmacological basis of vincristine lies in its interactions with various molecular targets, with the specific mechanisms as follows:

1. Inhibition of L-type calcium channels (VOCC)
   Vincristine alkali binds to VOCC to block calcium ion inflow into cells, lowers intracellular calcium concentration, regulates the contractile function of myocardium and vascular smooth muscle, and exerts antihypertensive and heart rate slowing effects.

2. Regulates tumor-related signaling pathways

3. AMPK (PRKAA1): As an energy-sensing enzyme, activation of AMPK promotes cellular metabolic homeostasis. Vincristine may influence tumor cell metabolism by regulating AMPK activity.
4. Anti-apoptotic proteins MCL1 and BCL2: Vincristine reduces the expression of these proteins and promotes tumor cell apoptosis.
5. NOTCH1 and STAT3 signaling pathways: Inhibit these pathways, blocking tumor cell proliferation and differentiation.
6. TOP1 and SIRT1: Affect DNA topoisomerase and deacetylase activities, interfering with DNA repair and stress responses in tumor cells.

7. NFE2L2 (NRF2): Regulates cellular antioxidant responses and affects the oxidative stress state of tumor cells.

8. Other targets
   Regulation of targets such as MAPT (microtubule-associated protein Tau) and IDH1 (isocitrate dehydrogenase 1) may participate in cytoskeletal reorganization and metabolic reprogramming, further affecting tumor cell survival and proliferation.

Through the synergistic action of multiple targets and pathways, vincristine alkaloid demonstrates a relatively complex and effective anti-tumor mechanism.

Druggability evaluation and pharmacokinetics

Druggability parameters

The molecular weight of vincristine alkaloid is 336.43, which fits the ideal range for small molecule drugs. Its LogP value of 3.1 indicates moderate lipid solubility, which facilitates cell membrane penetration and distribution in vivo. TPSA was 55.12 Ų, below 140 Ų, indicating good oral absorption potential. It has 4 hydrogen bond receptors, complies with Lipinski's rules, facilitating drug binding to targets.

Vincristine has high blood-brain barrier permeability, suggesting its potential for treating central nervous system diseases, but potential neurotoxicity risks should also be considered.

Toxicological evaluation

Currently, there is no definitive data on the hepatotoxicity, cardiotoxicity, and hERG channel inhibitory effects of vincristine alkaloids, requiring further systematic evaluation. The Ames test result was negative, indicating that it does not exhibit significant gene mutation induction and is relatively safe.

Pharmacokinetic characteristics

Pharmacokinetic studies of vincristine in existing literature are relatively limited. Its high lipophilubility and blood-brain barrier permeability suggest it is widely distributed in the body, possibly with rapid tissue distribution and metabolism. In the future, systematic in vivo absorption, distribution, metabolism, and excretion (ADME) studies are needed to clarify bioavailability, half-life, and metabolic pathways, providing a basis for clinical formulation design.

Prospects and outlooks for clinical applications

Vincristine, as an important active ingredient in alkaloids in the plant of vincris, possesses multi-target anti-cancer activity, especially showing potential therapeutic value for hematological malignancies such as leukemia. Its inhibitory effect on VOCs also shows potential in cardiovascular diseases, such as adjunctive treatment for hypertension and arrhythmias.

However, the clinical application of vincristine alkaloid is still in its early stages, presenting the following challenges:

1. Balancing efficacy and safety
   Further clarification of its effective dose range and toxic side effects is needed, especially systematic evaluation of cardiotoxicity and hepatotoxicity.

2. Pharmacokinetics optimization
   Improving in vivo stability and targeting through structural modification or drug carrier technology, thereby increasing bioavailability.

3. Combination medication strategies
   Explore combined use with other anticancer or cardiovascular drugs to achieve synergistic effects.

4. Preclinical and clinical research
   Strengthen animal model and clinical trial research to verify efficacy and safety, and promote their transformation into clinical drugs.

In the future, with advances in molecular biology and medicinal chemistry technologies, the mechanism of action of vincristine will be further elucidated, and its structural optimization and dosage form innovations will further promote its clinical application.

Conclusion

Vincristine alkaloid, a natural alkaloid derived from the periwinkle flower, shows broad application prospects in cancer and cardiovascular disease treatment due to its unique chemical structure and multi-target pharmacological activity. It exerts multiple biological effects by inhibiting L-type calcium channels and regulating multiple tumor-related signaling pathways. Although there are still certain challenges in druggability and clinical application, with deeper research, vincristine alkaloids are expected to become important candidate molecules for new anti-cancer and cardiovascular drugs. Future research should focus on safety evaluation, pharmacokinetic optimization, and clinical validation, promoting its transition from the laboratory to clinical practice to benefit patients.