Colchicum alkaloids

In addition, the alkaloid colchicine (from Colchicum autumnale) blocks tubulin polymerization by binding to heterodimeric (3-tubulin between amino acids 239 and 254. Since it inhibits the MT-dependent migration of granulocytes into areas of inflammation and their MT-dependent release of proinflammatory agents, it is used to treat attacks of gout. Its antimitotic effect in the gastrointestinal system induces diarrhoea. Nocodazole competes for the binding site of colchicine and has similar effects on heterodimeric (3-tubulin. 

Several groups of drugs that bind to tubulin at different sites interfere with its polymerization into microtubules. These drugs are of experimental and clinical importance (Bershadsky and Vasiliev, 1988). For example, colchicine, an alkaloid derived from the meadow saffron plant Colchicum autumnale or Colchicum speciosum), is the oldest and most widely studied of these drugs. It forms a molecular complex with tubulin in the cytosol pool and prevents its polymerization into microtubules. Other substances such as colcemid, podophyllotoxin, and noco-dazole bind to the tubulin molecule at the same site as colchicine and produce a similar effect, albeit with some kinetic differences. Mature ciliary microtubules are resistant to colchicine, whereas those of the mitotic spindle are very sensitive. Colchicine and colcemid block cell division in metaphase and are widely used in cytogenetic studies of cultured cells to enhance the yield of metaphase plate chromosomes. 

Colchicum alkaloids la 344,345,420 Collidine la 354 Concentration zone, TLC plates with la 56... 

Colchicine (6) was isolated by Pelletier and Caventou in 1820 and is the main alkaloid of the poisonous meadow saffron plant (Colchicum autum-nale L.) [12-16]. Following some considerable debate over colchicine s structure [17-20] and its successful synthesis [21-26], colchicine was found to bind to tubulin at what is referred to as the colchicine binding site [1,27]. 

Colchicine [Antigout Agent/Colchicum Alkaloid] Uses Acute gouty arthritis prevention of recurrences familial Mediterranean fever primary biliary cirrhosis Action -1- Migration of leukocytes X leukocyte lactic acid production Dose Initial 0.6—1.2 mg PO, then 0.6 mg ql-2h until rehef or GI SE develop (max 8 mg/d) do not r eat for 3 d /U 1-3 mg, then 0.5 mg q6h until rehef (max 4 mg/d) do not rqjeat for 7 d Prophylaxis PO 0.6 mg/d or 3-4 d/wk ... 

Colchicine is an alkaloid of Colchicum autumnale. Colchicine can produce dramatic relief from acute gout. Its mechanism of action is based on disappearance of microtubules in granulocytes, thereby inhibiting their migratory capacity, which is brought forward by the ability of colchicine to bind to tubulin. Colchicine is rapidly absorbed after oral administration and then metabolized to several metabolites which are excreted in the bile. Elimination from the body is slow. 

Although NSAIDs are now the first-line drugs for acute gout, colchicine was the primary treatment for many years. Colchicine is an alkaloid isolated from the autumn crocus, Colchicum autumnale. Its structure is shown in Figure 36-6. 

Colchicine is a poisonous tricyclic tropane alkaloid from the autumn crocus (Colchicum autumnale) and gloriosa lily (Gloriosa superba). This alkaloid is a potent spindle fiber poison, preventing tubulin polymerization.25 Colchicine has been used as an effective anti-inflammatory drug in the treatment of gout and chronic myelocytic leukemia, but therapeutic effects are attainable at toxic or near toxic dosages. For this reason, colchicine and its analogs are primarily used as biochemical tools in the mechanistic study of new mitotic inhibitors. 

Boye O and Brossi A (1992) Tropolonic Colchicum alkaloids and alio congeners. The Alkaloids, Chemistry and Pharmacology (ed Brossi A and Cordell GA) Vol 41. Academic, San Diego, pp 125-176. 

Colchicine is an alkaloid isolated from the autumn crocus, Colchicum autumnale. Its structure is shown in Figure 36-6. 

The chemistry and pharmacology of colchicine, the major alkaloid from Colchicum autumnale, have been repeatedly reviewed (/), and findings made since 1984 have been reported (2a-d). Recent developments in the... 

Extraction of dried plant materials from Colchicum species with methanol afforded, after separation into neutral and basic fractions and chromatography on silica, several tropolonic and alio congener alkaloids (listed in Table I and II). 

Two demethyl congeners of speciosine (1) were found in Colchicum ritchii from southern Jordan (4). The structures of these alkaloids, 2-demethylspeciosine (2), named speciocolchine, and 3-demethylspeciosine (3), named specioritchine, were elucidated by mass and H-NMR spectro-... 

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