Ansamycins inhibitors

An important family of inhibitors of procaryotic RNA synthesis are the antibiotics of the ansamycin series whose prototype is rifampicin. It inhibits bacterial RNA synthesis at the extremely low concentration of 0.01 Mg/ml (1.4 x 10-8 M) by binding to bacterial RNA polymerase35. ... 

Rifampicin was first shown by Hartmann et al. 54 to have a specific inhibitory effect on RNA polymerase from E. coli. Later, other active ansamycins were found and RNA polymerases from a large variety of bacteria other than E. coli proved to be sensitive to the drug. More recently, an RNA polymerase from E. coli containing only one subunit and probably involved in the initiation of DNA replication (dna G gene product) has been shown to be resistant to rifampicin5 s This holds true also for the various mammalian RNA polymerases. In contrast to non-specific inhibitors of transcription such as actinomycin and mitomycin, rifampicin interacts specifically with the bacterial enzyme itself. With the aid of 14C-labelled rifampicin it could be shown that the drug forms a very stable complex with the enzyme in a molar ratio of 1 1S6> 57 The dissociation constant of this complex is 10-9 M at 37 °C and... 

Maytansine s ansa macrolide structure shows noteworthy similarities to those of the rifamycins [255], streptovaricins [256], tolypomycins [257], and geldanamycin [258]. The ansamycin antibiotics and their derivatives have aroused considerable interest as antiviral and antimicrobial agents, and as inhibitors of RNA tumor virus reverse transcriptases. 

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. 

Moss, B. Ansamycins (A) Rifamycin SV Derivatives. In W. A. Carter (Edit.), Selective Inhibitors of Viral Functions, p. 313. Cleveland CRC Press, Inc. 1973. 

---