Ansamycin antibiotics antitumor activities

Among others, the ansamycin antibiotics have displayed antibacterial, antitumor and herbicidal activities. For many years, rifampicin, a semisynthesized antibiotic derived from rifamycin B, has been utilized for the treatment of tuberculosis. 

Among the naphthalenoid ansamycin antibiotics, the streptovaricin complex was reported to inhibit focus formation by MSV (MLV murine leukaemia virions) and to inhibit the splenomegaly-induced Rauscher leukaemia by virus selectively [226,227]. On the other hand, awamycin (26) [34,35] was shown to possess activity against HeLa S3 cells and antitumor activity against experimental murine tumors. Antitumor activity tests on streptovaricin C (44) were conducted [226,227]. 

An ansamycin antibiotic produced by Streptomyces spectabilis with antibacterial (against tuberculosis pathogens), antiviral, and antitumor activities. S. occurs as a multi-component mixture of up to ten individual compounds (S. A to G, J, K, and U) with S. C (methyl streptovaricate, C4oH5,NO,4, Mr 769.84, amorphous, mp. 189-191 °C, [a][) 4-602°) as the main component. The S. are inhibitors of bacterial RNA-polyme-rase as well as the reverse transcriptase of oncogenic viruses. The biosynthesis of the aromatic core branches off from the shikimic acid pathway while the alkyl chain is formed on the polyketide pathway. 

Polyketide and non-ribosomal peptides produced by bacteria and fungi often attain the conformations that establish biological activity by cychzation constraints introduced by tailoring enzymes. This includes heterocychzation of cysteines, serines and threonines in non-ribosomal peptides. The second cychzation constraint is macrocychzation in polyketides, such as the above-mentioned antibiotic erythromycin and the antitumor epothilones. Regio- and stereospecific macrocychzation usuaUy occurs at the end of the polyketide and non-ribosomal peptide assembly hnes during chain release by thioesterase domains [49]. However, in the case of antibiotics of the ansamycin class, like the antitubercular drug rifamycin, the final... 

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