The emergence of multidrug resistant bacterial pathogens and the increase of antimicrobial resistance constitutes a major health challenge, leading to intense research efforts being focused on the discovery of novel antimicrobial compounds. In this study, endophytes were isolated from different parts of Sandwithia guyanensis plant (leaves, wood and latex) belonging to the Euphorbiaceae family and known to produce antimicrobial compounds, and chemically characterised using Molecular Network in order to discover novel antimicrobial molecules. One fungal endophyte extract obtained from S. guyanensis latex showed significant antimicrobial activity with Minimal Inhibitory Concentration on methicillin-resistant Staphylococcus aureus at 16 µg/mL. The chemical investigation of this fungus (Lecanicillium genus) extract led to the isolation of 5 stephensiolides compounds, four of which demonstrated antibacterial activity. Stephensiolide I and G showed the highest antibacterial activity on MRSA with a MIC at 4 and 16 µg/mL respectively.Plants 2020, 9, 47 2 of 11 chemical constituents of a wide variety of extracts in a single map [5,6]. Furthermore, MN offers the possibility to map additional information, such as biological, analytical and taxonomical details over networks [6][7][8]. In this study, we applied a related multi-informative prioritisation strategy based on the use of MN, with the aim of finding new antimicrobial structures from of a set of extracts from 42 Euphorbiaceae endophytes.The Euphorbiaceae family comprises approximately 283 genera and 7300 species, and has been found in various morphological types, including herbs, shrubs and trees [9]. Some species of the family are used as lubricants and purgatives, while others are used as a source of medicinal drugs for the treatment of diarrhoea, inflammation and swelling. Their milky latex secretions impart several toxic effects such as dermatitis, severe irritation to the eyes and stomach discomfort. Moreover, Euphorbia sp. latex has been shown to possess moderate antimicrobial properties and ability to protect against herbivores [10]. Together, the antimicrobial, insecticidal and toxicity properties of Euphorbia latex makes it a hostile environment for microbes and plant-feeding insect pests. However, it has been recently highlighted that Euphorbia sp. latex contains unexpectedly complex bacterial and fungal communities [11]. Meanwhile, endophytes, which are microorganisms residing in plant tissues without inducing any diseases in the host plants, have been shown to defend themselves as well the plants from pathogens and have a crucial role in plant survival. They also improve the ecological adaptability of the hosts by enhancing their tolerance to environmental stresses and resistance to phytopathogens and/or herbivores [12]. In addition, endophytes residing within plants may produce identical or similar secondary metabolites as their host plant, and therefore, have also been recognised as a potential source of novel bioactive molecules. These common compounds ...

A screening of 57 entomopathogenic microorganisms against human pathogens was subjected to mass spectrometry molecular networking-based dereplication. A particular strain of fungus, Isaria farinosa BSNB-1250, producing potentially both active and novel metabolites, was grown on a large-scale on potato dextrose agar (PDA) medium. Paecilosetin (1) and five new analogues (2-6) were isolated. The structures of the new compounds were elucidated using 1D and 2D NMR. The absolute configurations of compounds 1-6 were determined by Mosher ester derivatives (1), comparison of experimental and calculated ECD spectra (2-4 and 6), and singlecrystal X-ray diffraction analysis (5). Compounds 1-6 were assayed against methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, Candida albicans, Trichophyton rubrum and the MRC-5 cell line. Compounds 1 and 5 exhibited strong antibacterial activity against MSSA and MRSA with MIC values of 1-2 µg/mL.