Rifamycin
Rifamycins are macrocyclic lactams, it refers to a group of antibiotics produced by bacteria of the family of Pseudonocardiaceae ( in the order of Actinomycetales ), especially of the genus Amycolatopsis. But they can also be produced synthetically. Rifamycins are effective against gram-positive bacteria, especially against bacteria of the genus Mycobacterium. See especially in the therapy of tuberculosis, leprosy, and the atypical tuberculosis, Mycobacterium avium complex ( MAC) use. The most important representative of the group is rifampicin.
Discovery
The rifamycins were first isolated in 1957 by the fermentation of Amycolatopsis mediterranei in a laboratory of Gruppo Lepetit SpA in Milan by Piero Sensi and Phinehas Margalith. They discovered seven different rifamycins, rifamycin which they called A, B, C, D, E, S and SV. Amycolatopsis mediterranei was at that time still under the name Streptomyces mediterranei known, the species was only in 1986 assigned to the correct genus. Molecular biological studies from 2004 to the rifamycin - producing bacterial strains led to the realization that they represent a separate species, which is known as Amycolatopsis rifamycinica.
Rifamycin B first found commercial use. The company Lepetit let the substance in 1958 in the United Kingdom and in 1959 patented in the United States. The drug quickly found widespread use in the treatment of tuberculosis in the 1960s.
Rifamycin derivatives
In 1966, Lepetit under the name rifampicin, an orally applicable rifamycin on the market. 1975 rifabutin developed a derivative of rifamycin S, which came on the U.S. market in 1991. Rifapentine was from Hoechst Marion Roussel ( now Sanofi -Aventis ) developed in 1999. Rifaximin, a semisynthetic derivative of rifamycin, is a bactericidal oral broad-spectrum antibiotic that acts only in the intestine.
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 hence the initiation of the chain formation. Through the suppression of RNA transcription, protein synthesis is inhibited, ultimately. The effect of rifamycins is bactericidal.