Abstract
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 CC50 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.
Highlights
Antibiotic resistant bacteria have become a major threat to global health and there is an urgent need for new antibacterial drugs [1]
Because of the diversity of antimicrobial compounds produced by bacteria and fungi, natural product based antibiotics still dominate over the purely synthetic ones when comparing antibacterial drugs developed and introduced since 1981 [3]
The improvements include the development of high-performance liquid chromatography (HPLC) and, more recently, ultra-high performance liquid chromatography (UHPLC) for efficient isolation/separation of natural products in complex mixtures, and high-resolution mass spectrometry (HRMS) techniques and cryogenic nuclear magnetic resonance (NMR) probes for structure determination of small amounts of natural products [4,5]
Summary
Antibiotic resistant bacteria have become a major threat to global health and there is an urgent need for new antibacterial drugs [1]. Because of the diversity of antimicrobial compounds produced by bacteria and fungi, natural product based antibiotics still dominate over the purely synthetic ones when comparing antibacterial drugs developed and introduced since 1981 [3]. The improvements include the development of high-performance liquid chromatography (HPLC) and, more recently, ultra-high performance liquid chromatography (UHPLC) for efficient isolation/separation of natural products in complex mixtures, and high-resolution mass spectrometry (HRMS) techniques and cryogenic nuclear magnetic resonance (NMR) probes for structure determination of small amounts of natural products [4,5].
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