The continued emergence of multi-drug-resistant bacteria is a major public health concern. The identification and development of new antibiotics, especially those with new modes of action, is imperative to help treat these infections. This review lists the 22 new antibiotics launched since 2000 and details the two first-in-class antibiotics, fidaxomicin (1) and bedaquiline (2), launched in 2011 and 2012, respectively. The development status, mode of action, spectra of activity, historical discovery and origin of the drug pharmacophore (natural product, natural product derived, synthetic or protein/mammalian peptide) of the 49 compounds and 6 β-lactamase/β-lactam combinations in active clinical development are discussed, as well as compounds that have been discontinued from clinical development since 2011. New antibacterial pharmacophore templates are also reviewed and analyzed.

/pdf/antibiotics-in-the-clinical-pipeline-in-2013-2rwtbfhz6s.pdf

Antibiotics in the clinical pipeline in 2013

A literature survey covering more than twenty-three thousand bioactive microbial products including eight thousand antiinfectives demonstrated the increasing relevance of the so called 'rare' actinomycetes as a source of new antibiotics. Past and present efforts in the isolation of rare actinomycetes have enriched the Biosearch Italia Strain Collection with more than twenty thousand strains, showing that, when selective isolation methods are developed and extensively applied, some genera, such as Actinomadura, Actinoplanes, Micromonospora, Microtetraspora, are not rare at all and can be recovered from many soil samples. The current focus is on the isolation of members of Streptosporangiaceae family, given their promising chemical diversity.

https://link.springer.com/content/pdf/10.1023/A:1010287600557.pdf

Rare genera of actinomycetes as potential producers of new antibiotics

Natural products have served as powerful therapeutics against pathogenic bacteria since the golden age of antibiotics of the mid-20th century. However, the increasing frequency of antibiotic-resistant infections clearly demonstrates that new antibiotics are critical for modern medicine. Because combinatorial approaches have not yielded effective drugs, we propose that the development of new antibiotics around proven natural scaffolds is the best short-term solution to the rising crisis of antibiotic resistance. We analyze herein synthetic approaches aiming to reengineer natural products into potent antibiotics. Furthermore, we discuss approaches in modulating quorum sensing and biofilm formation as a nonlethal method, as well as narrow-spectrum pathogen-specific antibiotics, which are of interest given new insights into the implications of disrupting the microbiome.

Natural Products as Platforms To Overcome Antibiotic Resistance

A systematic analysis of all naturally-occurring glycosylated bacterial secondary metabolites reported in the scientific literature up through early 2013 is presented. This comprehensive analysis of 15 940 bacterial natural products revealed 3426 glycosides containing 344 distinct appended carbohydrates and highlights a range of unique opportunities for future biosynthetic study and glycodiversification efforts.

/pdf/a-comprehensive-review-of-glycosylated-bacterial-natural-4txxvyk4h3.pdf

A comprehensive review of glycosylated bacterial natural products.

The emergence of multi-drug-resistant bacteria and the lack of new antibiotics in the antibiotic drug development pipeline, especially those with new modes of action, is a major health concern. This review lists the 20 new antibiotics launched since 2000 and records the 40 compounds currently in active clinical development. Compounds in the pipeline from new antibiotic classes are reviewed in detail with reference to their development status, mode of action, spectrum of activity and lead discovery. In addition, the NP or synthetic derivation is discussed, with activity against Gram-negative bacteria highlighted.

/pdf/antibiotics-in-the-clinical-pipeline-in-2011-1omyfag34m.pdf

Antibiotics in the clinical pipeline in 2011.

By a combination of chemical degradations and 1H and 13C n.m.r. studies, the structure of the antibiotic lipiarmycin, produced by Actinoplanes deccanensis, has been elucidated. The molecule contains two glycosyl moieties, namely 2-O-methyl-4-O-homodichloro-orsellinate-β-D-rhamnose and 4-O-isobutyrate-5-methyl-β-rhamnose, attached to a 18-membered unsaturated lactone ring.

Structure elucidation of the macrocyclic antibiotic lipiarmycin

Actinoplanes deccanensis ATCC 21983, the producer of antibiotics lipiarmycin A3 and A4, furnished also a related antibiotic designated lipiarmycin B, active against Gram-positive bacteria, including anaerobes, and against Neisseria. The structures of the two major components, B3 and B4, were elucidated from their physico-chemical properties, 1H and 13C NMR spectra and fast atom bombardment mass spectra data in comparison with lipiarmycins A3 and A4.

B. Cavalleri

Papers

Structure elucidation of the macrocyclic antibiotic lipiarmycin

Structure and biological activity of lipiarmycin B.

Structure Elucidation of the Macrocyclic Antibiotic Lipiarmycin.