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 .
Scientific Research Applications
Vincristine has a wide range of scientific research applications, particularly in the fields of chemistry, biology, medicine, and industry . In chemistry, it is used as a model compound for studying the mechanisms of alkaloid biosynthesis and the development of new synthetic methodologies . In biology, this compound is used to study cell division and the effects of microtubule inhibition on cellular processes . In medicine, it is a key component of chemotherapy regimens for various cancers, helping to inhibit the growth and spread of cancer cells . In industry, this compound is used in the development of new drug formulations and delivery systems to improve its efficacy and reduce side effects .
Mechanism of Action
Target of Action
Vincristine, a vinca alkaloid, primarily targets the protein tubulin, a key component of the microtubules in cells . Microtubules play a crucial role in maintaining cell structure and function, particularly during cell division .
Mode of Action
This compound binds to tubulin, inhibiting the polymerization of tubulin dimers and preventing the formation of microtubules . This interaction disrupts the formation of the mitotic spindle, a structure essential for chromosome separation during cell division . As a result, cells are arrested at metaphase, a stage in mitosis, leading to cell death .
Biochemical Pathways
The primary biochemical pathway affected by this compound is the cell cycle, specifically the M and S phases . By disrupting microtubule dynamics, this compound causes mitotic arrest, halting the cell cycle and leading to cell death . This disruption can also interfere with amino acid, cyclic AMP, and glutathione metabolism, as well as calmodulin-dependent Ca2±transport ATPase activity, and cellular respiration .
Pharmacokinetics
The pharmacokinetics of this compound involve its absorption, distribution, metabolism, and excretion (ADME). This compound is administered intravenously, bypassing the absorption phase . It is metabolized primarily in the liver by the CYP3A5 enzyme . This compound’s neurotoxicity, a dose-limiting factor, is thought to be influenced by genetic variations in drug-metabolizing enzymes and transporters .
Result of Action
The molecular effect of this compound’s action is the disruption of microtubule formation, leading to cell cycle arrest . On a cellular level, this results in the death of rapidly dividing cells, particularly cancer cells . This can also affect healthy cells, leading to side effects such as peripheral neuropathy .
Action Environment
Environmental factors can influence the action and efficacy of this compound. For instance, the presence of other drugs used in combination therapies can impact this compound’s effectiveness and toxicity profile . Additionally, genetic variations in patients can influence the drug’s metabolism and transport, potentially affecting its efficacy and toxicity .
Safety and Hazards
Vincristine may harm an unborn baby. Use effective birth control to prevent pregnancy, and tell your doctor if you become pregnant . It is vital that it not be given intrathecally, as this may kill . Avoid dust formation. Avoid breathing mist, gas or vapours. Avoid contacting with skin and eye. Use personal protective equipment. Wear chemical impermeable gloves. Ensure adequate ventilation. Remove all sources of ignition. Evacuate personnel to safe areas. Keep people away from and upwind of spill/leak .
Future Directions
In the future, baseline quantitative PET-CT can be used to predict prognosis in PMBCL . Engineered yeast brews precursors of anticancer drug vinblastine . This cytotoxic drug was first discovered in 1985 and found useful in cancer therapy . It is administered intravenously as a chemotherapeutic agent for management of various types of melanomas including lung cancer, lymphocyte-based leukaemia, glioblastomas, and acute myeloid leukaemia .
Biochemical Analysis
Biochemical Properties
Vincristine is a vinca alkaloid that binds to the microtubular proteins of the mitotic spindle . This interaction leads to the crystallization of the microtubule and mitotic arrest or cell death . This compound has some immunosuppressant effect . The vinca alkaloids are considered to be cell cycle phase-specific .
Cellular Effects
This compound works by stopping the cancer cells from separating into 2 new cells, thereby stopping the growth of the cancer . It achieves this through a process that disrupts the formation of microtubules, which affects cell division and eventually leads to apoptosis .
Molecular Mechanism
The molecular mechanism of this compound involves its binding to the tubulin protein, stopping the tubulin dimers from polymerizing to form microtubules . This causes the cell to be unable to separate its chromosomes during the metaphase . The cell then undergoes apoptosis . The this compound molecule inhibits leukocyte production and maturation .
Temporal Effects in Laboratory Settings
It is known that within 15 to 30 minutes after injection, over 90% of the drug is distributed from the blood into tissue, where it remains tightly, but not irreversibly, bound .
Dosage Effects in Animal Models
In animal models, this compound has shown high efficiency (86.6%) for treatment of transmissible venereal tumor in canines at the dose of 0.5 mg/m^2 of body surface (IV), on 7-14 days intervals . One tumor (6.6%) was refractory to this compound, while at the treatment beginning a mass reduction was observed .
Metabolic Pathways
This compound may interfere with amino acid, cyclic AMP, and glutathione metabolism . It may also interfere with calmodulin-dependent Ca^2+ -transport ATPase activity, cellular respiration, and nucleic acid and lipid biosynthesis .
Transport and Distribution
This compound is transported and distributed within cells and tissues primarily through the bloodstream . It is given intravenously and can be administered through a drip into the arm or hand . Over 90% of the drug is distributed from the blood into tissue within 15 to 30 minutes after injection .
Subcellular Localization
The subcellular localization of this compound is primarily at the mitotic spindle, where it binds to the microtubular proteins . This binding leads to the crystallization of the microtubule and mitotic arrest or cell death .
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 .
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
| { "Design of the Synthesis Pathway": "The synthesis pathway of Vincristine involves a series of chemical reactions that convert starting materials into the final product. The key steps in the pathway include the formation of key intermediates, such as catharanthine and vindoline, which are then combined to form Vincristine. The synthesis pathway is complex and involves several steps, each of which requires careful optimization and control to ensure high yields and purity of the final product.", "Starting Materials": [ "Catharanthine", "Vindoline", "Methyl vinyl ketone", "Acetic anhydride", "Bromine", "Hydrogen chloride", "Sodium hydroxide", "Hydrogen gas", "Palladium on carbon" ], "Reaction": [ "Step 1: Conversion of Catharanthine to 3',4'-didehydro-4'-deoxy-Catharanthine using Bromine", "Step 2: Conversion of 3',4'-didehydro-4'-deoxy-Catharanthine to 3'-hydroxy-4'-deoxy-Catharanthine using Hydrogen chloride", "Step 3: Conversion of Vindoline to 3'-hydroxy-4'-methoxy-Vindoline using Methyl vinyl ketone and Acetic anhydride", "Step 4: Combination of 3'-hydroxy-4'-deoxy-Catharanthine and 3'-hydroxy-4'-methoxy-Vindoline to form Vindoline", "Step 5: Conversion of Vindoline to Vincristine using Sodium hydroxide and Hydrogen gas in the presence of Palladium on carbon catalyst" ] } | |
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 |
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 |
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 |
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 |
| 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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Please be aware that all articles and product information presented on BenchChem are intended solely for informational purposes. The products available for purchase on BenchChem are specifically designed for in-vitro studies, which are conducted outside of living organisms. In-vitro studies, derived from the Latin term "in glass," involve experiments performed in controlled laboratory settings using cells or tissues. It is important to note that these products are not categorized as medicines or drugs, and they have not received approval from the FDA for the prevention, treatment, or cure of any medical condition, ailment, or disease. We must emphasize that any form of bodily introduction of these products into humans or animals is strictly prohibited by law. It is essential to adhere to these guidelines to ensure compliance with legal and ethical standards in research and experimentation.
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