Novel antibiotics SF2738A,B and C, and their analogs produced by Streptomyces sp.

Abstract

Three new antibiotics SF2738A,B and C, and their analogs were isolated from the culture broth of Streptomyces sp. The antibiotics are active against Gram-positive bacteria, Gram-negative bacteria and fungi, and exhibited cytotoxic activity against P388 murine leukemia cells with IC50 values of 0.08, 0.25 and 7.5 /ig/ml, respectively. Their structures were determined by spectral analyses and chemical conversion. Especially, the structure of SF2738Awas confirmed to be (£)-((4-methoxy-5-methylthio-2-(2-pyridyl)pyridin-6-yl)methylene)azanol by X-ray crystallographic analysis.

Antifungal Actinomycete Metabolites Discovered in a Differential Cell-Based Screening Using a Recombinant TOPO1 Deletion Mutant Strain

“…The identity of compounds 1 and 2 with collismycins A and B, respectively, was proven by mass spectroscopy and two-dimensional 1 H-NMR spectroscopy, supported by a search in a natural products database [9] . The spectral data are in accordance with those reported in the literature [10,11] .…”

“…Besides their antifungal effects, several other bioactivities (antibacterial, cytotoxic, dexamethasone-glucocorticoid receptor binding inhibition) were previously reported for compounds 1 and 2 [10,11] . Therefore, these structurally unique sulfur-containing microbial alkaloids cannot be regarded as selective antifungal agents, and no further evaluation of their bioactivities was carried out.…”

Engineering the Biosynthesis of the Polyketide-Nonribosomal Peptide Collismycin A for Generation of Analogs with Neuroprotective Activity

“…Overall, several biologic activities have been associated with members of this family of natural products such as antibacterial, antifungal, and cytotoxic activities (Gomi et al, 1994;Stadler et al, 2001) and they also have potential as anti-inflammatory agents through binding to the glucocorticoid receptor (Shindo et al, 1994) or as neuroprotectants by reducing oxidative stress in neurons (Martinez et al, 2007). Using labeled precursors, lysine-derived picolinic acid (PA) has been proposed to be a precursor for the biosynthesis of these compounds (McInnes et al, 1979;Vining et al, 1988).…”

“…Collismycin A ( Figure 1A) is a member of the 2,2 0 -bipyridyl family of natural products that also includes SF2738B-F (Gomi et al, 1994), pyrisulfoxins (Tsuge et al, 1999), and caerulomycins (Funk and Divekar, 1959;McInnes et al, 1977McInnes et al, , 1978. Overall, several biologic activities have been associated with members of this family of natural products such as antibacterial, antifungal, and cytotoxic activities (Gomi et al, 1994;Stadler et al, 2001) and they also have potential as anti-inflammatory agents through binding to the glucocorticoid receptor (Shindo et al, 1994) or as neuroprotectants by reducing oxidative stress in neurons (Martinez et al, 2007).…”

Proteomic profiling reveals that collismycin A is an iron chelator

“…Collismycin A (CMA), a natural product produced by Streptomyces sp., is an antibiotic and has cytotoxic activity against cancer cells13141516. In this study, we use ChemProteoBase profiling to show that collismycin A acts as an iron chelator17.…”