Labradorins with Antibacterial Activity Produced by Pseudomonas sp.

The urgent need for new antibacterial drugs has led to renewed interest in microorganisms, which historically have been the main source of previously discovered antibiotics. The present study describes the discovery of two new antibacterial oxazolylindole type alkaloids, labradorins 5 (1) and 6 (2), which were isolated and characterized from two isolates of Pseudomonas sp., along with four previously known tryptophane derived alkaloids. The structures of 1 and 2 were determined by NMR spectroscopy and MS, and confirmed by synthesis. During bioassay-guided isolation using several human bacterial pathogens, 1 and 2 displayed activity towards Staphylococcus aureus and Acinetobacter baumannii. The minimal inhibitory concentrations (MIC) of compounds 1 and 2 against S. aureus were 12 μg·mL(−1) and 50 μg·mL(−1), respectively, whereas the MICs against A. baumannii were >50 μg·mL(−1). The CC(50) values of compound 1 towards a liver cell line (HEP-G2) and a T-cell line (MT4) were 30 μg·mL(−1) and 20 μg·mL(−1), respectively, and for compound 2 were >100 μg·mL(−1) and 20 μg·mL(−1), respectively. Due to the limited potency of compounds 1 and 2, along with their toxicity, the compounds do not warrant further development towards new antibiotics.