Vincristine
Overview
Description
Vincristine is a vinca alkaloid derived from the Madagascar periwinkle plant, Catharanthus roseus . It is a chemotherapy medication used to treat various types of cancer, including acute lymphocytic leukemia, Hodgkin’s disease, non-Hodgkin’s lymphoma, neuroblastoma, and small cell lung cancer . This compound works by inhibiting cell division, making it a crucial component in cancer treatment regimens .
Preparation Methods
Vincristine is primarily obtained from the natural alkaloid plant source, Catharanthus roseus . The extraction process involves isolating the compound from the plant material, followed by purification steps to obtain the active ingredient . Industrial production methods often involve the use of advanced extraction techniques and purification processes to ensure the compound’s efficacy and safety .
Chemical Reactions Analysis
Vincristine undergoes various chemical reactions, including oxidation, reduction, and substitution . Common reagents used in these reactions include oxidizing agents, reducing agents, and nucleophiles . The major products formed from these reactions depend on the specific conditions and reagents used . For example, oxidation of this compound can lead to the formation of different oxidized derivatives, while reduction can yield reduced forms of the compound .
Scientific Research Applications
Clinical Applications
Vincristine is approved for treating various malignancies, including:
- Acute Lymphoblastic Leukemia (ALL)
- Hodgkin's and Non-Hodgkin Lymphomas
- Neuroblastoma
- Wilms Tumor
- Rhabdomyosarcoma
- Kaposi Sarcoma
FDA-Approved Indications
| Cancer Type | FDA Approval Year |
|---|---|
| Acute Lymphoblastic Leukemia | 1963 |
| Wilms Tumor | 1963 |
| Hodgkin's Lymphoma | 1963 |
| Non-Hodgkin Lymphoma | 1963 |
| Rhabdomyosarcoma | 1963 |
Off-Label Uses
In addition to its approved indications, this compound is used off-label for:
- Central Nervous System (CNS) tumors
- Ewing Sarcoma
- Medulloblastoma
- Bladder Cancer
- Ovarian Cancer
Combination Therapies
This compound is often used in combination with other chemotherapeutic agents to enhance efficacy while minimizing adverse effects. Notable combination regimens include:
- CHOP : Cyclophosphamide, Doxorubicin, this compound, Prednisolone
- CVP : Cyclophosphamide, this compound, Prednisolone
- CISCA : Cisplatin, Doxorubicin, Vinblastine, Bleomycin
Case Studies and Clinical Trials
Numerous studies underscore this compound's effectiveness across different cancer types. A notable trial reported that this compound administered weekly to children with advanced cancer resulted in a 68% objective tumor response rate across various malignancies, including ALL and Hodgkin's disease .
Clinical Trial Insights
| Study Focus | Findings |
|---|---|
| This compound in Advanced Cancer | 68% response rate in pediatric patients |
| Combination Therapy with this compound | Enhanced efficacy in lymphoma treatments |
Pharmacokinetics and Challenges
This compound's pharmacokinetic profile reveals rapid distribution and significant protein binding (approximately 75%). However, its clinical use is limited by neurotoxicity and other side effects such as alopecia and constipation. Recent advancements focus on improving its delivery through nanotechnology-based formulations to enhance targeting and reduce toxicity .
Emerging Trends
Research continues to explore this compound's role in combination therapies and novel formulations. For instance, liposomal formulations like Marqibo have been developed to prolong circulation time and improve dosing efficacy for patients with relapsed ALL . Additionally, ongoing studies are investigating its use in treating solid tumors and enhancing its therapeutic index through innovative drug delivery systems .
Mechanism of Action
Vincristine exerts its effects by binding to tubulin, a protein that is essential for the formation of microtubules . By inhibiting microtubule formation, this compound disrupts the mitotic spindle, leading to cell cycle arrest at the metaphase stage . This inhibition of cell division ultimately results in the death of rapidly dividing cancer cells . Additionally, this compound may interfere with nucleic acid and protein synthesis by blocking the utilization of glutamic acid .
Comparison with Similar Compounds
These compounds share a similar mechanism of action, targeting microtubule formation and inhibiting cell division . vincristine is unique in its specific clinical applications and its relatively lower bone marrow suppression compared to other vinca alkaloids . Vinblastine, for example, is used to treat different types of cancer and has a different toxicity profile . Vindesine and vinflunine are also used in cancer treatment but have distinct pharmacokinetic properties and clinical uses .
Properties
CAS No. |
57-22-7 |
|---|---|
Molecular Formula |
C46H56N4O10 |
Molecular Weight |
825.0 g/mol |
IUPAC Name |
methyl (10S,11R,12R)-11-acetyloxy-12-ethyl-4-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-methoxycarbonyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9-tetraen-13-yl]-8-formyl-10-hydroxy-5-methoxy-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraene-10-carboxylate |
InChI |
InChI=1S/C46H56N4O10/c1-7-42(55)22-28-23-45(40(53)58-5,36-30(14-18-48(24-28)25-42)29-12-9-10-13-33(29)47-36)32-20-31-34(21-35(32)57-4)50(26-51)38-44(31)16-19-49-17-11-15-43(8-2,37(44)49)39(60-27(3)52)46(38,56)41(54)59-6/h9-13,15,20-21,26,28,37-39,47,55-56H,7-8,14,16-19,22-25H2,1-6H3/t28-,37?,38?,39-,42+,43-,44?,45+,46+/m1/s1 |
InChI Key |
OGWKCGZFUXNPDA-DLBZMDDPSA-N |
impurities |
3'-hydroxyvincristine; 4'-deoxyvincristine; N-desmethylvinblastine; deacetylvincristine; deacetylvinblastine; vinblastine; leurosine; formylleurosine |
SMILES |
CCC1(CC2CC(C3=C(CCN(C2)C1)C4=CC=CC=C4N3)(C5=C(C=C6C(=C5)C78CCN9C7C(C=CC9)(C(C(C8N6C=O)(C(=O)OC)O)OC(=O)C)CC)OC)C(=O)OC)O |
Isomeric SMILES |
CC[C@@]1(C[C@@H]2C[C@@](C3=C(CCN(C2)C1)C4=CC=CC=C4N3)(C5=C(C=C6C(=C5)C78CCN9C7[C@@](C=CC9)([C@H]([C@@](C8N6C=O)(C(=O)OC)O)OC(=O)C)CC)OC)C(=O)OC)O |
Canonical SMILES |
CCC1(CC2CC(C3=C(CCN(C2)C1)C4=CC=CC=C4N3)(C5=C(C=C6C(=C5)C78CCN9C7C(C=CC9)(C(C(C8N6C=O)(C(=O)OC)O)OC(=O)C)CC)OC)C(=O)OC)O |
Appearance |
White to off-white, odorless amorphous or crystalline powder |
Color/Form |
Blades from methanol |
melting_point |
424 to 428 °F (NTP, 1992) 218-220 °C |
Key on ui other cas no. |
57-22-7 |
physical_description |
Vincristine appears as a white crystalline solid. Melting point 218 °C. Used as an antineoplastic. |
shelf_life |
STERILE SOLN IN EITHER H2O OR PHYSIOLOGICAL SALINE STORED IN REFRIGERATOR FOR UP TO 2 WK WITHOUT SIGNIFICANT LOSS OF POTENCY |
solubility |
WHITE TO SLIGHTLY YELLOW, AMORPHOUS OR CRYSTALLINE POWDER; ODORLESS, HYGROSCOPIC; FREELY SOL IN WATER /VINCRISTINE SULFATE USP/ |
Synonyms |
cellcristin Citomid Farmistin Leurocristine Oncovin Oncovine Onkocristin PFS, Vincasar Sulfate, Vincristine Vincasar Vincasar PFS Vincristin Bristol Vincristin medac Vincristine Vincristine Sulfate Vincrisul Vintec |
Origin of Product |
United States |
Retrosynthesis Analysis
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Strategy Settings
| Precursor scoring | Relevance Heuristic |
|---|---|
| Min. plausibility | 0.01 |
| Model | Template_relevance |
| Template Set | Pistachio/Bkms_metabolic/Pistachio_ringbreaker/Reaxys/Reaxys_biocatalysis |
| Top-N result to add to graph | 6 |
Feasible Synthetic Routes
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