New functionally substitutes cyclopropanecarboxylic acids as ethylene biosynthesis innovative regulators

Abstract

Background: Derivatives of small carbocycles (cyclobutanes and cyclopropanes) are known as bioactive molecules. Both their natural and synthetic representatives have multiple applications. Particularly, 1-aminocyclopropane-1-carboxylic acid (ACC) serves as the well-studied ethylene biosynthesis precursor. The development of new functionally substituted cyclopropane carboxylic acids, which show promise as effective inhibitors of ethylene biosynthesis, is crucial for regulating the plant cycle and preserving the quality of fruits and vegetables. 

Objectives: This research focused on the in-silico studies aimed at developing a universal and affordable methodology for synthesizing new analogs of ACC and assessing their modulating activity on ethylene biosynthesis in plants. The findings from this in silico research provide a foundation for the upcoming in vitro studies. 

Results: The elaborated efficient catalytic system [Cu(I) salt/amine/DMSO] enabled the synthesis of model compounds under mild conditions, resulting in increasing yields up to quantitative levels. For bioactivity preliminary assessment we performed in silico research of newly synthesized (E)-2-phenyl-1-chlorocyclopropane-1-carboxylic acid and drug-design an appropriate 1-amino-derivative as the inhibitor of 1-aminocyclopropane-1-carboxylate oxidase 2 (ACO2) of Arabidopsis thaliana. Docking results showed certain advantages of the newly synthesized compound in comparison to well-known inhibitors of ethylene biosynthesis.

Conclusions: The recommended synthetic technology has increased efficiency in yield quantification. In silico studies, a high affinity for ACO2 has been demonstrated. The synthesized compounds exhibit superior characteristics compared to widely used market preparations for regulating ethylene biosynthesis. More detailed comparative in vitro studies are planned. 

Keywords: plant growth regulation, cyclopropane carboxylic acids, ethylene biosynthesis inhibitors, molecular docking, atom transfer radical addition (ATRA), Cu(I) Complex catalyst.