143-67-9

An anticancer drug. White to slightly yellow crystalline powder.

This compound is sensitive to light, hydrolysis, oxidation, and heat. VINBLASTINE SULFATE(143-67-9) is very hygroscopic. .

Water soluble..Rapidly hydrolyzes.

SYMPTOMS: Symptoms of exposure to this chemical include temporary mental depression, paresthesias, loss of deep-tendon reflexes, headache, convulsions, psychoses; dysfunction of the autonomic nervous system, with marked constipation, paralytic ileus, urinary retention, bilateral pain and tenderness of the parotid glands associated with dryness of the mouth, sinus tachycardia; nausea, vomiting, anorexia, diarrhea; loss of hair, vesicular mucositis of the mouth, and dermatitis.

Flash point data for this chemical are not available; however VINBLASTINE SULFATE is probably combustible.

Vinblastine, derived from C. roseus, also known as V. rosea, a Madagascar periwinkle, is an antimicrotubule drug used to treat certain cancers, including Hodgkin’s lymphoma, non-small cell lung, breast, head and neck, and testicular cancer. Like its chemical analog vincristine, vinblastine binds tubulin, inhibiting the assembly of microtubules and causing M phase-specific cell cycle arrest by disrupting microtubule assembly and proper formation of the mitotic spindle. It has been shown to inhibit steady-state tubulin addition to microtubules with a K_i value of 0.18 μM, inhibit B16 melanoma cell proliferation with an IC₅₀ value of 1 nM, and produce complete inhibition of L-cell proliferation at 40 nM. Vinblastine is reported to be an effective component of certain chemotherapy regimens, particularly when used with bleomycin and methotrexate in vinblastine, bleomycin, and methotrexate combination chemotherapy for Stage IA or IIA Hodgkin lymphomas.

Crystalline Solid

Velban ,Lilly ,US ,1961

antineoplastic, spindle poison

Labelled Vinblastine (V314000). Antitumor alkaloid isolated from periwinkle, Vinca rosea Linn., Apocynaceae; inhibits microtubule assembly. An antineoplastic.

Vinblastin sulfate USP (Velban) is used to treat Hodgkin’s disease; lymphosarcoma; reticulum cell sarcoma; neuroblastoma; choriocarcinoma; carcinoma of breast, lung, oral cavity, testis, bladder; acute and chronic leukemia; histiocytosis; mycosis fungoides.

ChEBI: Vincaleukoblastine sulfate is an alkaloid sulfate salt. It is functionally related to a vincaleukoblastine.

According to US Patent 3,225,030, 1,500 grams of dried ground plant of Vinca rosea were intimately mixed with 1,000 ml of a 2% tartaric acid solution, and the mixture was extracted with three 9-liter portions of benzene. The benzene extracts were combined and were concentrated in vacuo to about 1,500 ml. The concentrate was mixed with 1 liter of 2% tartaric acid and the mixture was steam-distilled under reduced pressure until all of the benzene had distilled over. The insoluble residue was dissolved in hot methanol, a second 1-liter portion of 2% tartaric acid solution was added, and the mixture was steam-distilled under reduced pressure until all of the methanol had distilled.
The undistilled aqueous tartaric acid solution was extracted with three 1-liter portions of ethylene dichloride, and was then brought to a pH of about 8.5 to 9.5 by the addition of 28% aqueous ammonium hydroxide. The ammoniacal solution was extracted with three 1-liter portions of ethylene dichloride; the ethylene dichloride extracts were combined, were dried, and were evaporated in vacuo, yielding a residue of 3.35 grams of a light-brown powder.
1 1/2 grams of the residue were dissolved in 10 ml of benzene, and the solution was passed over a chromatographic adsorption column containing 50 grams of alumina (Alcoa activated alumina, Grade F-20) which had previously been shaken for about 20 minutes with a mixture of 100 ml of benzene containing 1.5 ml of 10% acetic acid.
The column was developed by washing it with 2,100 ml of benzene. The column was then washed sequentially with 300 ml of benzene-chloroform solvent (95:5 by volume) and 800 milliliters of benzene-chloroform solvent (75:25) to remove indeterminate impurities. The leurosine was eluted from the alumina by passing over the column 900 ml of benzene chloroform solvent (50:50).
The eluate was evaporated to dryness in vacuo, leaving an amorphous residue of 113 mg of leurosine. The residue was treated with a few ml of methanol in which it quickly dissolved, but from which leurosine quickly precipitated in crystalline form. Because of the affinity of leurosine for water, and the presence of traces of water in the solvents, the leurosine was obtained in the form of its octahydrate. Although the material as obtained was substantially pure, it was further purified by recrystallizing it from hot methanol solution. The hydrated leurosine obtained decomposed at about 200° to 205°C.
Further elution of the above chromatographic column with a 50:50 benzene- chloroform solvent mixture or with a 25:75 benzene-chloroform solvent mixture serves to elute vincaleukoblastine. Vincaleukoblastine also occurs in the latter fractions containing leurosine. Vincaleukoblastine is obtained from vincaleukoblastine-containing fractions by evaporation to dryness, either of a filtrate from which leurosine has previously been isolated, or from a chromatographic eluate fraction. The resulting residue is dissolved in ethanol and 286 ethanolic sulfuric acid is added until the pH is lowered to about 4. The solution is seeded with crystals of vincaleukoblastine sulfate and is chilled for about 24 hours. Vincaleukoblastine sulfate, if present, precipitates during this period and can be separated by filtration. Vincaleukoblastine sulfate melts at about 284° to 285°C.

Velban (Lilly).

Cancer chemotherapy

Anticancer agent; microtubule disrupter. Induces apoptosis in cultured hepatocytes and human lymphoma cells.

Primary TargetInteraction of tubulin with microtubule-associated proteins, specifically Tau and MAP2

Antineoplastic agent

The major toxic effect of vinblastine is a dose-related bone marrow depression. This is more frequent and severe than with the close structural analog, vincristine. Dose-related leukopenia occurs with a nadir of 4 to 10 days and with recovery occurring over another 7 to 14 days. Because of the relatively predictable nadir, it may be possible to administer vinblastine cautiously as often as every 7 to 10 days. Thrombocytopenia typically occurs; however, with standard dosing regimens, serious platelet depressions are infrequent. Erythrocytes are usually only slightly depressed.

Vinblastine may be employed in the treatment of lymphomas, carcinomas, mastocytomas, and splenic tumors in small animals. It is more effective than vincristine in the treatment of canine mast cell tumors.

Potentially hazardous interactions with other drugs
Aldesleukin: avoid concomitant use.
Antibacterials: toxicity increased by erythromycin - avoid; possible increased risk of ventricular arrhythmias with delamanid.
Antiepileptics: phenytoin levels may be reduced.
Antifungals: possible increased risk of toxicity with itraconazole; metabolism possibly inhibited by posaconazole (increased risk of neurotoxicity).
Antimalarials: avoid with piperaquine with artenimol.
Antipsychotics: avoid with clozapine (increased risk of agranulocytosis).

Vinblastine is extensively metabolised mainly in the liver by the CYP3A group of isoenzymes to desacetylvinblastine, which is more active than the parent compound. 33
% of the drug is slowly excreted in the urine and 21
% in the faeces within 72 hours.

Store at -20°C

Crystallise the sulfate from MeOH or EtOH and dry it in vacuo over conc H2SO4. The free base crystallises from EtOH or MeOH m 211-216o (+ 2MeOH .1 H2O) and forms a stable etherate from Et2O with m 201-211o, and [] D +42o (CHCl3), and UV max at 214 and 259nm (log  4.73 and 4.21). The dihydrochloride has m 244-246o(dec)(MeOH). It is a monoamine oxidase B inhibitor and induces microtubule aggregation. It is an antineoplastic drug for Hodgkin’s lymphoma. [Neuss et al. J Am Chem Soc 81 4754 1959, Jong-KeunSon et al. J Med Chem 33 1845 1990, Warfield & Bouck Science 186 1219 1974, Beilstein 26 III/IV 3167.]

Vinblastine binds to tubulin and inhibits microtubule assembly. This inhibition prevents mitotic spindle formation and results in an accumulation of cells in metaphase.
Vinblastine is considered cell cycle phase specic for mitosis; however, the cytotoxic effect probably occurs in S phase and is expressed only in M phase. At high doses, direct effects may be expressed in S and G1 phases. Vinblastine is assumed to have stathmokinetic (cell cycle arrest) effects similar to vincristine.

1) Hamel?et al. (1996),?Antimitotic natural products and their interactions with tubulin; Med. Res. Rev.,?16?207 2) Tsukidate?et al. (1993),?Microtubule antagonists activate programmed cell death (apoptosis) in cultured rat hepatocytes; Am. J. Pathol.,?143?918 3) Satori?et al. (2013),?Describing autophagy via analysis of individual organelles by capillary electrophoresis with laser induced fluorescence detection; Anal. Chem.,?85?11391 4) Caron and Herwood (2007),?Vinblastine, a chemotherapeutic drug, inhibits palmitoylation of tubulin in human leukemic lymphocytes; Chemotherapy,?53?51