Addition of ethylamines to the phenols of bithionol and synthetic retinoids does not elicit activity in gram-negative bacteria

Ana V. Cheng, Cassandra L. Schrank, Iliana E. Escobar, Eleftherios Mylonakis, William M. Wuest

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Our labs have demonstrated the activity of bithionol and synthetic retinoids against methicillin-resistant Staphylococcus aureus (MRSA), as well as their membrane-acting mechanism of action. However, the compounds lack activity in gram-negative species. Herein, we apply a known strategy for converting gram-positive agents into broad-spectrum therapies: addition of an alkylamine. By appending an alkylamine to the phenols of these known membrane disruptors, we test whether this approach is applicable to our compounds. Ultimately, biological testing in four MRSA strains and three gram-negative species showed abolished or diminished activity in all our analogs compared to their parent compounds and no gram-negative activity. Thus, we find that alkylamines would not elicit broad-spectrum activity from bithionol or CD437 derivatives.

Original languageEnglish (US)
Article number127099
JournalBioorganic and Medicinal Chemistry Letters
Volume30
Issue number9
DOIs
StatePublished - May 1 2020

Keywords

  • Bithionol
  • CD437
  • Gram-negative bacteria
  • Methicillin-resistant Staphylococcus aureus
  • Retinoid

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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