57-22-7 Usage
Chemical Description
Vincristine is a hydrophobic antitumor drug used to treat various types of cancer.
Description
A complex dimeric alkaloid isolated from Vinca minor, this base has the structure
given above based upon chemical and spectroscopic data. It resembles
Vinblastine in its pharmacological action. Depending on the dosage, it causes
either thrombocytosis with no effect upon the leucocytes, or thrombocytopenia
accompanied by peucopenia in rats. Thrombocytosis persists even after prolonged
treatment with drugs given in the correct dosage.
Chemical Properties
solid
Physical properties
Appearance: needlelike crystals were produced when recrystallized by methanol.
The other properties of vincristine are similar to vinblastine.
History
Vinblastine and vincristine were extracted from vinca, and researchers found that they are the main ingredient of vinca which have antitumor activity. This is an accidental harvest by hard work and inspiration during scientific research process.
It was firstly reported as an important discovery by Annals of the New York Academy of Sciences, and one report was published by Robert Noble and Charles Thomas Beer . They demonstrated that vinblastine can cause severe leukopenia.
In 1963, vincristine (trade name, Oncovin) developed by Eli Lilly was approved by the US FDA, it provided a good choice for tumor chemotherapy program and gradually became the essential tumor chemotherapy drugs.
At the early stages of the study, vinblastine and vincristine are directly extracted from the vinca, but the cost is high, and the extraction efficiency is low . Especially the specific chiral monomer compounds with biological activity are difficult to obtain. In the following years, the researchers used genetic engineering, biosynthesis, chemical synthesis, and other technical methods to explore and optimize the production process of vinblastine drugs. In particular, the rise of asymmetric synthesis provides a more economical choice for the synthesis of vinblastine compounds and increases productivity to more than 22% . At the same time, the pharmaceutical dosage forms were developed from the beginning as simple sulfate injection to liposomal preparations and nanoparticle preparations, which improve the efficacy, reduce adverse reactions, and play better antitumor effect.
Uses
Antineoplastic[Note—Graphic formula same as for Vinblastine Sulfate, except that R is CHO].
Indications
It was recorded in the Pharmacopoeia of the People’s Republic of China (2015), the
British Pharmacopoeia (2017), the United States Pharmacopeia (40), the Japanese
Pharmacopoeia (17th ed.), the European Pharmacopoeia (9th ed.), and The
International Pharmacopoeia (5th ed.).Vincristine sulfate injection is used to treat leukemia, lymphadenoma, non-small
cell lung cancer, nephroblastoma, and neuroblastoma in clinical practice generally,
but the effect of vinblastine is better than vincristine in Hodgkin lymphoma
treatment.
Therapeutic Function
Cancer chemotherapy
General Description
A white crystalline solid. Melting point 218°C. Used as an antineoplastic.
Health Hazard
Highly toxic, may be fatal if inhaled, swallowed or absorbed through skin. Avoid any skin contact. Effects of contact or inhalation may be delayed. Fire may produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution.
Fire Hazard
Flash point data for Vincristine are not available, but Vincristine is probably combustible.
Pharmacology
Vinblastine drugs have a strong inhibitory effect on monozygotic leukemia, breast
cancer, liver cancer, ovarian cancer, head and neck cancer, testicular cancer, solid
sarcoma, and malignant melanin in a variety of spontaneous or transplanted lymphocytic leukemias. Although the structure of vinblastine and vincristine is very
similar, there are some differences in pharmacological effects, and there is no crossresistance .The mechanism of vinblastine and vincristine is similar as cell cycle-specific
antineoplastic agents. They all inhibit tubulin polymerization, interfere spindle
microtubule formation, block the cell cycle in M phase, and then inhibit the proliferation of cancer cells . X-ray diffraction results showed that Vinblastine targets
at the hydrophobic structure on tubulin, Vinblastine inserted into the trough as the
wedge, blocking the polymerization of tubulin, making a spirochete structure of
tubulin itself form, and loss of biological role . However, this antitumor effect
can affect other rapid proliferation cells, and then small intestinal epithelial cells
and bone marrow cells will be inhibited, which is one of the reasons of gastrointestinal side effects and bone marrow transplantation side effects. The effect of vincristine is better than vinblastine, and the dosage is lower, the probability and intensity
of side effects are lower. Recently, it has been found that vinblastine and vincristine
can also suppress growth of tumor cell by inhibiting the synthesis of RNA and
protein.
Clinical Use
Vincristine is an important component of the curative
combination chemotherapy for acute lymphoblastic
leukemia, Hodgkin’s disease (the MOPP regimen),
and non-Hodgkin’s lymphomas. It is also used in several
regimens for pediatric solid tumors, including Wilms’ tumor,
Ewing’s sarcoma, rhabdomyosarcoma, and neuroblastoma;
in adult tumors of the breast, lung, and
cervix; and in sarcomas. Its relative lack of myelosuppression
makes it more attractive than vinblastine for
use in combination with myelotoxic drugs.Vinblastine is
especially useful in testicular carcinomas and is also active
in Hodgkin’s disease, other types of lymphomas,
breast cancer, and renal cell carcinoma.
Side effects
All vinca alkaloids are severe vesicants that can induce necrosis, cellulitis, and/or thrombophlebitis. Proper needle placement before administration should be assured to eliminate the risk of extravasation. Unlike the tissue damage caused by the vesicant action of nitrogen mustards and antibiotic antineoplastics, cold exacerbates tissue destruction. If extravasation occurs, apply heat for 1 hour fours time a day for 3 to 5 days, coupled with local hyaluronidase injections. Vinca alkaloids are all Category D teratogens and are fatal if administered by the intrathecal route.
References
Mokry et al., Experientia, 18, 564 (1962)
Pharmacology:
Chandorkar.,lnd. J. Physiol. Pharmacol., 17, 105 (1973)
Check Digit Verification of cas no
The CAS Registry Mumber 57-22-7 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 7 respectively; the second part has 2 digits, 2 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 57-22:
(4*5)+(3*7)+(2*2)+(1*2)=47
47 % 10 = 7
So 57-22-7 is a valid CAS Registry Number.
InChI:InChI=1/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
57-22-7Relevant articles and documents
Synthesis of vinca alkaloids and related compounds. Part XCIII. Skeletal rearrangement of cyclovinblastine derivatives: Formation of a novel bisindole system
Honty, Katalin,Demeter, ádám,Szántay Jr., Csaba,Hollósi, Miklós,Kolonits, Pál,Szántay, Csaba
, p. 169 - 194 (1999)
Bisindole alkaloids of the vinblastine (VLB) type can be oxidized to give a Ψ-aspidosperma-aspidosperma type skeleton via 3'-7'-transannular cyclization. Acid catalysis triggers an aspidospermane→eburnane skeletal rearrangement of these cyclic derivatives, thus giving a novel bisindole system with a Ψ-eburnea-aspidosperma type skeleton. A previously unexplored aspect of this transformation is the observed retention or inversion at C(16') depending on the starting C(16') configuration. The present paper gives a detailed account of the synthetic aspect of this work together with preliminary NMR and CD results concerning the epimerization at C(16').
Biosynthesis of the indole alkaloids. Cell-free systems from Catharanthus roseus plants
Kutney,Choi,Honda,et al.
, p. 2088 - 2101 (2007/10/02)
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