Maytansinoid alkaloids

The cause of the cell cycle specificity of the bisindole alkaloids may be associated with the ability of these compounds to interact with the protein tubulin and thereby inhibit the polymerization (and depolymerization) of microtubules (16,17). In this respect the cellular pharmacology of vinca alkaloids is similar to that of other cytotoxic natural products such as colchicine or podophyllotoxin. On closer inspection, however, Wilson determined that the specific binding site on tubulin occupied by vinblastine or vincristine is chemically distinct from the site occupied by the other natural products (18). Subsequent experiments have determined that the maytansinoids, a class of ansa-macrocycles structurally distinct from the bisindoles, may bind to tubulin at an adjacent (or overlapping) site (19). A partial correlation of the antimitotic activity of these compounds with their tubulin binding properties has been made, but discrepancies in cellular uptake probably preclude any quantitative relationship of these effects (20). 

It contains alkaloids among which are (he maytansinoids, which have had considerable interest as antitumor agents. Samples (165) of 92 species gave the following as positives previously known Calha edulis (2/3), Euonymus atropurpureus, Hippocratea indica, Maylenus mossamhicensis. 

These alkaloids were named as ansamitocins, and the chemical structures of ansamitocins P-1,2, 3, 3, and 4 are shown in the figure. These alkaloids are based on ansamitocin P-0, a common parent skeleton, by a reductive hydrolysis of ansamitocins P-1,2,3,3, and 4 using LiAlH4. Ansamitocin P-0 corresponds to maytansinol, which is the parent skeleton of the above-mentioned maytansine. On the other hand, it was found that ansamitocins P-1 and P-2 isolated from Maytenus plants corresponded to maytanacine and maytansinol propionate, respectively [7].The alkaloids possessing the maytansinol (ansamitocin P-0) skeleton are also referred to as maytansinoids. The synthesis of maytansinol (ansamitocin P-0) as a racemic mixture has been reported [8]. 

Other Sources of Imidazole Alkaloids Lythraceae alkaloids Maytansinoids Antitumor Activity Other Biological Activity Muscarine Alkaloids Naphthylisoquinoline Alkaloids Peptide Alkaloids Purine or Xanthine Alkaloids Biosynthesis... 

While it is unclear about the involvement of maytansinoids in interactions between plants and bacteria or fungi there is ample evidence concerning the interesting phenomenon of fungal endophyte-produced alkaloids. Considerable literature has become available recently demonstrating that associations... 

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