Paecilosetin Derivatives as Potent Antimicrobial Agents from Isaria farinosa

  • J Nat Prod. 2020 Oct 23;83(10):2915-2922. doi: 10.1021/acs.jnatprod.0c00444.
Orianne Brel  1 ,  Seindé Touré  1 ,  Marceau Levasseur  1 ,  Christian Lechat  2 ,  Léonie Pellissier  3  4 ,  Jean-Luc Wolfender  3  4 ,  Elsa Van-Elslande  1 ,  Marc Litaudon  1 ,  Isabelle Dusfour  5  6 ,  Didier Stien  7 ,  Véronique Eparvier  1
Affiliations
  • 1. Université Paris-Saclay, CNRS, Institut de Chimie des Substances Naturelles, UPR 2301, 91198, Gif-sur-Yvette, France.
  • 2. ASCOFrance, 79360, Villiers-en-bois, France.
  • 3. School of Pharmaceutical Sciences, University of Geneva, CMU, 1211 Geneva 4, Switzerland.
  • 4. Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, CH-1211 Geneva 4, Switzerland.
  • 5. Institut Pasteur de la Guyane, Unité de Contrôle et Adaptation des Vecteurs, BP6010, 97306 Cayenne, France.
  • 6. Département de Santé Globale, Institut Pasteur, 75015, Paris, France.
  • 7. Laboratoire de Biodiversité et Biotechnologies Microbiennes (LBBM), Observatoire Océanologique, Sorbonne Universités, UPMC Univ. Paris 06, CNRS, 66650 Banyuls-sur-Mer, France.
PMID: 33021377 DOI: 10.1021/acs.jnatprod.0c00444
Abstract

Fifty-seven entomopathogenic Microorganisms were screened against human pathogens and subjected to mass spectrometry molecular networking based dereplication. Isaria farinosa BSNB-1250, shown to produce potentially novel biologically active metabolites, was grown on a large scale on potato dextrose agar, and paecilosetin (1) and five new analogues (2-6) were subsequently isolated. The structures of the new compounds were elucidated using 1D and 2D NMR. The absolute configurations of compounds 1-6 were determined using Mosher ester derivatives (1, 3, 4), comparison of experimental and calculated ECD spectra (2-4 and 6), and single-crystal X-ray diffraction analysis (5). Compounds 1 and 5 exhibited strong Antibacterial activity against MSSA and MRSA with MIC values of 1-2 μg/mL.