Synthesis and Exploration of Abscisic Acid Receptor Agonists Against Dought Stress by Adding Constraint to a Tetrahydroquinoline-Based Lead Structure

Guido Bojack, Rachel Baltz, Jan Dittgen, Christian Fischer, Jörg Freigang, Rahel Getachew, Erwin Grill, Hendrik Helmke, Sabine Hohmann, Gudrun Lange, Stefan Lehr, Fabien Porée, Jana Schmidt, Dirk Schmutzler, Zhenyu Yang, Jens Frackenpohl

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

New oxotetrahydroquinolinyl- and oxindolinyl sulfonamides interacting with RCAR/(PYR/PYL) receptor proteins were identified as lead structures against drought stress in crops starting from protein docking studies of a sulfonamide lead structure, followed by in-depth SAR studies. Optimized five to six step synthetic approaches via substituted amino oxo-tetrahydro-quinolines and amino oxo-indolines as essential intermediates gave access to the envisaged oxo-tetrahydroquinolinyl and oxindolinyl sulfonamides. Whilst oxo-tetrahydroquinolinyl sulfonamides with additional carbon substituents or spiro-cycloalkyl groups exhibited only low to moderate target affinities, the corresponding spiro-oxindolinyl and oxo-tetrahydroquinolinyl sulfonamides carrying optimized N-substituents revealed strong interactions with RCAR/(PYR/PYL) receptor proteins in Arabidopsis thaliana. Remarkably, the in vitro activity observed for these new compounds was on the same level as observed for the naturally occurring plant hormone in line with strong efficacy against drought stress in-vivo (canola and wheat as broad-acre crops).

Original languageEnglish
Pages (from-to)3442-3457
Number of pages16
JournalEuropean Journal of Organic Chemistry
Volume2021
Issue number23
DOIs
StatePublished - 21 Jun 2021

Keywords

  • Abscisic acid receptor proteins
  • Drought stress
  • Indolines
  • Phytochemistry
  • Tetrahydroquinolines

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