Identifying new lead structures to enhance tolerance towards drought stress via high-throughput screening giving crops a quantum of solace

Bioorg Med Chem. 2019 Dec 15;27(24):115142. doi: 10.1016/j.bmc.2019.115142. Epub 2019 Oct 19.

Abstract

Novel synthetic lead structures interacting with RCAR/(PYR/PYL) receptor proteins were identified based on the results of a high-throughput screening campaign of a large compound library followed by focused SAR studies of the three most promising hit clusters. Whilst indolinylmethyl sulfonamides 8y,z and phenylsulfonyl ethylenediamines 9y,z showed strong affinities for RCAR/ (PYR/PYL) receptor proteins in wheat, thiotriazolyl acetamides 7f,s exhibited promising efficacy against drought stress in vivo (wheat, corn and canola) combined with confirmed target interaction in wheat and arabidopsis thaliana. Remarkably, binding affinities of several representatives of 8 and 9 were on the same level or even better than the essential plant hormone abscisic acid (ABA).

Keywords: Aryl sulfonamides; Drought stress; High throughput screening; Phytochemistry; Thiotriazolyl acetamides.

MeSH terms

  • Abscisic Acid / analogs & derivatives*
  • Abscisic Acid / chemistry
  • Abscisic Acid / pharmacology
  • Crops, Agricultural
  • Droughts
  • Drug Discovery
  • Gene Expression Regulation, Plant / drug effects
  • High-Throughput Screening Assays
  • Molecular Structure
  • Plant Growth Regulators / chemistry*
  • Plant Growth Regulators / pharmacology*
  • Plant Proteins / chemistry*
  • Plant Proteins / genetics
  • Plant Proteins / metabolism
  • Protein Binding
  • Sulfonamides
  • Triticum / genetics
  • Triticum / metabolism

Substances

  • Plant Growth Regulators
  • Plant Proteins
  • Sulfonamides
  • Abscisic Acid