Colchicum autumnale colchicine from

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. 

Podophyllotoxin (38) Podophyllum peltatum L.), colchicine (9) Colchicum autumnale L.), vinblastine (4), and vincristine (5) Catharan-thus roseus (L.) G. Don] are standard microtubule-destabilizing agents used in cancer research. Paclitaxel (21), from Taxus brevifolia Nutt., acts as a promoter of stabilization of microtubules and causes mitotic arrest in an unusual fashion. ... 

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... 

Compared with extracts, pure compounds undoubtedly guarantee a more precise and reproducible dosage and are the only acceptable form of administration of active principles characterised by an extremely narrow therapeutic window, such as the plant alkaloid colchicine 40 from Colchicum autumnale L. Lethal poisoning from colchicine has been reported upon ingestion of 3-4 times the therapeutic dose of this compound111 and it would, therefore, be impractical to use colchicine-rich extracts rather than their active principle. 

Alkaloids are not limited to those natural products which are basic in character. For example, colchicine isolated from Colchicum autumnale (Ldiaceae) and used for the treatment of gout, etc. is not basic because the nitrogen atom in the molecule is present in a neutral amide group. However, the biosynthetic precursor of colchicine is autumnaline, a typical, basic phenethylisoquinoline alkaloid. Therefore any compound derived from such an intermediate should be classified as an alkaloid. 

Results obtained in the National Cancer Institute of the USA from the study of the cytostatic activity of the (133) and bis(chloroethyl)amino derivatives on 60 tumor lines were reported [138]. Originally colchicine a soluble alkaloid was extracted from Colchicum autumnale also known as autumn crocus, meadow saffron or itkuchala in Uzbekistan which means dog poison [138]. 

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. 

YAMADA M, KOBAYASHi Y, FURUOKA H, MATSUIT (2000) Comparison of enterotoxicity between autumn crocus (Colchicum autumnale L.) and colchicine in the guinea pig and mouse enterotoxicity in the guinea pig differs from that in the mouse. . 1 Vet Med Sci. 62 809-13. 

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. 

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

The natural compound colchicine (1) was extracted from the poisonous meadow saffron Colchicum autumnale L. and was the first antimitotic destabilizing agent to be discovered [9], It consists of three rings a trimethoxyphenyl (TMP, ring A), a... 

The alkaloid colchicine (FI) isolated from the medicinal plant Colchicum autumnale L. (Liliaceae family) still is used to treat gout and familial Mediterranean fever. FI and thiocolchicine (F2) (SCH3 rather than OCH3 at C-10), which is more stable and more potent but slightly more toxic, are mitotic inhibitors that inhibit polymerization of tubulin (69). Although they show antileukemic activity, they are too toxic to use as anticancer agents, which prompts the synthesis of new, less toxic analogs. 

LOIC C Colchicum and demecolchicine Colchicine is an alkaloid, previously extracted from the seeds of the Autumn Crocus or Meadow-saffron, Colchicum autumnale L., but nowadays from the seeds of Gloriosa,... 

This mode of action is not unique since the natural product colchicine, from the autumn crocus Colchicum autumnale (once used as a treatment for gout), also binds to tubulin and disrupts microtubule assembly. It was never seriously considered as an anti-cancer drug owing to its low therapeutic index that is, the dose required to produce clinical benefit was not much greater than the dose causing serious adverse effects or even death. A third plant product with similar biological properties, podophyllotoxin from the American Mayapple, provided the stimulus for research that led to the discovery of another excellent anti-cancer drug - etoposide. 

All garden enthusiasts know about the nice autumn crocus (Colchicum autumnale), which flowers in late autumn. It is not difficult to understand that this very conspicuous plant profits by containing a strong poison that protects it from pathogens and herbivores. It contains colchicine, which is very toxic and has a complicated structure. The substance is well known to plant breeders because it is used to double the number of chromosomes artificially in plants. A synthetic benzimidazole derivative, l-methyl-3-dode-cylbenzimidazolium chloride, was developed in 1960 as a curative fungicide against apple scab. Thiabendazole, another synthetic benzimidazole derivative, has been used as an anthelmintic since 1962. 

Also mentioned in the aforecited book are colchicine and colchidnamide, derived from the common autumn crocus (Colchicum autumnale), also called meadow saffron. (Colchicine, incidentally, is used in plant gaieties to artificially produce mutations.) The notable use cited is against breast cancer, but gout and arthritis also yield to treatment. It is emphasized that both these alkaloids are potent, and their use requires expert medical supervision. Another plant mentioned is cro-talaria (Crotalaria spectabilis), from which a toxic alkaloid called monocrotaline may be obtained. This substance also has antitumor properties, but acts against the liver. 

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