Discovery and Characterization of Fluopipamine, a Putative Cellulose Synthase 1 Antagonist within Arabidopsis

B. Kirtley Amos, Victoria Pook, Erica Prates, Jozsef Stork, Manesh Shah, Daniel A. Jacobson, Seth DeBolt

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Herbicide-resistant weeds are increasingly a problem in crop fields when exposed to similar chemistry over time. To avoid future yield losses, identifying herbicidal chemistry needs to be accelerated. We screened 50,000 small molecules using a liquid-handling robot and light microscopy focusing on pre-emergent herbicides in the family of cellulose biosynthesis inhibitors. Through phenotypic, chemical, genetic, and in silico methods we uncovered 6-{[4-(2-fluorophenyl)-1-piperazinyl]methyl}-N-(2-methoxy-5-methylphenyl)-1,3,5-triazine-2,4-diamine (fluopipamine). Symptomologies support fluopipamine as a putative antagonist of cellulose synthase enzyme 1 (CESA1) from Arabidopsis (Arabidopsis thaliana). Ectopic lignification, inhibition of etiolation, phenotypes including loss of anisotropic cellular expansion, swollen roots, and live cell imaging link fluopipamine to cellulose biosynthesis inhibition. Radiolabeled glucose incorporation of cellulose decreased in short-duration experiments when seedlings were incubated in fluopipamine. To elucidate the mechanism, ethylmethanesulfonate mutagenized M2 seedlings were screened for fluopipamine resistance. Two loci of genetic resistance were linked to CESA1. In silico docking of fluopipamine, quinoxyphen, and flupoxam against various CESA1 mutations suggests that an alternative binding site at the interface between CESA proteins is necessary to preserve cellulose polymerization in compound presence. These data uncovered potential fundamental mechanisms of cellulose biosynthesis in plants along with feasible leads for herbicidal uses.

Original languageEnglish
Pages (from-to)3171-3179
Number of pages9
JournalJournal of Agricultural and Food Chemistry
Issue number6
StatePublished - Feb 14 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Published by American Chemical Society.


  • CESA
  • cellulose synthase
  • chemical genomics
  • herbicides
  • inhibitor
  • plant cell wall

ASJC Scopus subject areas

  • General Chemistry
  • General Agricultural and Biological Sciences


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