Semi-synthetic zwitterionic rifamycins: a promising class of antibiotics; survey of their chemistry and biological activities

Abstract

Rifamycins are an important group of macrocyclic antibiotics highly active against tuberculosis and various other Gram-positive pathogenic bacteria. Naturally occurring rifamycins, gained from Streptomyces varieties, display a moderate anti-bacterial activity. Some definite modifications performed at the naphthol chromophore of their complex macrolactam backbone led to new active and stable semi-synthetic rifamycins. The increasing resistance phenomena documented worldwide and the high anti-bacterial potential of new semi-synthetic derivatives are the main drive for the search for new rifamycins. Interestingly, many anti-bacterial drugs extracted from Streptomyces strains display remarkable zwitterionic structural features. However relatively few explicit reports on dipolar, zwitterionic rifamycin derivatives are known; what can be seen as peculiar considering the high antibacterial activity of the most established compound of this class: rifampicin. The aim of this survey is to give a general overview on the rifamycins antibiotics, to underline the zwitterionic character of successful antibiotics and to focus more specifically on available zwitterionic semi-synthetic rifamycins and whose biological activities against tuberculosis and various other mycobacteria infections.