Rifamycins

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Rifamycins are macrocyclic lactams, it refers to a group of antibiotics , of bacteria from the family of Pseudonocardiaceae (in the order of Actinomycetales be generated), especially of the genus Amycolatopsis . But they can also be produced synthetically. Rifamycins act against various bacteria, especially against bacteria from the genus of mycobacteria . They are used in particular in the treatment of tuberculosis , leprosy and the atypical tuberculosis, Mycobacterium Avium Complex (MAC). The most important representative of the group is rifampicin .

Rifamycins contain a lactam ring

discovery

The first rifamycins were isolated in 1957 by the fermentation of Amycolatopsis mediterranei in a laboratory of Gruppo Lepetit SpA in Milan by Piero Sensi and Pinhas Margalith . They discovered seven different rifamycins, which they named rifamycin A, B, C, D, E, S, and SV. Amycolatopsis mediterranei was then still known under the name Streptomyces mediterranei , the species was only assigned to the correct genus in 1986. Molecular biological investigations from 2004 on the rifamycin-producing bacterial strains led to the realization that these represent a species of their own called Amycolatopsis rifamycinica .

Rifamycin B first found commercial use. The company Lepetit was the substance in 1958 in the UK and 1959 in the United States patent . The drug quickly found widespread use in the treatment of tuberculosis in the 1960s.

Rifamycin derivatives

In 1966 Lepetit launched an orally administered rifamycin under the name Rifampicin . In 1975, rifabutin, a derivative of rifamycin S, was developed, which came on the US market in 1991. Rifapentin was developed in 1999 by Hoechst Marion Roussel (now Sanofi-Aventis ). Rifaximin , a semi-synthetic derivative of rifamycin, is a broad spectrum bactericidal oral antibiotic that works only in the gut.

Mechanism of action

Like other antibiotics of the rifamycin group, rifamycins bind irreversibly to the beta subunit of the prokaryotic DNA-dependent RNA polymerase. In this way it blocks the binding of the enzyme to the DNA and thus the initiation of chain formation. By suppressing RNA transcription, protein synthesis is ultimately inhibited. The effects of rifamycins are bactericidal.

Individual evidence

  1. ^ Jean Euzéby, Aidan C. Parte: Genus Amycolatopsis. In: List of Prokaryotic names with Standing in Nomenclature ( LPSN ). Retrieved February 20, 2014 .
  2. ↑ P. Sensi, P. Margalith, MT Timbal: Rifomycin, a new antibiotic; preliminary report . In: Il Farmaco: Edizione Scientifica . tape 14 , no. 2 , 1959, p. 146-147 , PMID 13639988 .
  3. ↑ S. Bala, R. Khanna et al. a .: Reclassification of Amycolatopsis mediterranei DSM 46095 as Amycolatopsis rifamycinica sp. nov. In: International journal of systematic and evolutionary microbiology. Volume 54, No. 4, July 2004, pp. 1145-1149, doi : 10.1099 / ijs.0.02901-0 . PMID 15280283 .
  4. ↑ LL Brunton, JS Lazo, KL Parker (eds.): Goodman & Gilman's The pharmacological basis of therapeutics . 11th edition. McGraw-Hill, New York 2006.
  5. ↑ P. Gionchetti, F. Rizzello, A. Venturi, F. Ugolini, M. Rossi, P. Brigidi, R. Johansson, A. Ferrieri, G. Poggioli, M. Campieri: Review-antibiotic treatment in inflammatory bowel disease: rifaximin, a new possible approach . In: European Review for Medical and Pharmacological Sciences . tape 3 , no. 1 , 1999, p. 27-30 , PMID 10710827 .

literature

  • Vladimir Prelog, Wolfgang Oppolzer: Ansamycine, a new class of microbial metabolic products . In: Helvetica Chimica Acta . tape 56 , no. 7 , 1973, p. 2279-2287 , doi : 10.1002 / hlca.19730560716 .
  • Ansgar Stratmann: The biology of the ansamycins: example rifamycin . In: BIOspectrum . tape 3 , 2004, p. 249-253 ( online [PDF]).
  • Patent US3150046 . ‌