5-Alkyl-1,2,3,4-tetrahydroquinolines, new membrane-interacting lipophilic metabolites produced by combined culture of Streptomyces nigrescens and Tsukamurella pulmonis

Org Lett. 2015 Apr 17;17(8):1918-21. doi: 10.1021/acs.orglett.5b00607. Epub 2015 Mar 31.

Abstract

Eight novel 5-alkyl-1,2,3,4-tetrahydroquinolines (5aTHQs) bearing different side chains have been isolated from a combined culture of Streptomyces nigrescens HEK616 and Tsukamurella pulmonis TP-B0596. The chemical structures including the absolute configuration were elucidated by spectroscopic analysis and total synthesis. 5aTHQs inhibited the growth of wild-type fission yeast while only weakly inhibiting the growth of several mutant strains synthesizing premature ergosterol. These results demonstrate that 5aTHQs are novel antifungals that may target cell membranes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinomycetales / chemistry
  • Actinomycetales / metabolism*
  • Antifungal Agents / chemistry
  • Antifungal Agents / metabolism
  • Antifungal Agents / pharmacology
  • Dose-Response Relationship, Drug
  • Lipids / chemistry*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Quinolines / chemistry
  • Quinolines / metabolism*
  • Quinolines / pharmacology*
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / metabolism
  • Streptomyces / chemistry
  • Streptomyces / metabolism*
  • Structure-Activity Relationship

Substances

  • Antifungal Agents
  • Lipids
  • Quinolines
  • 1,2,3,4-tetrahydroquinoline