Epoxy tetrahydrophthalimides as potential bioactive agents: synthesis and computational study

Area of Science:

• Organic Chemistry
• Agrochemistry
• Biochemistry

Background:

• Growing weed resistance to herbicides necessitates the discovery of new bioactive substances.
• Imides are a class of compounds with known biological activities, including herbicidal properties.
• This study focuses on epoxy tetrahydrophthalimides, exploring their synthesis and bioactivity.

Purpose of the Study:

• To synthesize, purify, and elucidate the structure of novel epoxy tetrahydrophthalimides.
• To evaluate the phytotoxicity and herbicidal potential of the synthesized compounds.
• To investigate potential biological targets of these imides using in silico methods.

Main Methods:

• A four-step synthetic route involving a microwave-assisted Diels-Alder reaction.
• Phytotoxicity assays using germination tests on various plant species (Lactuca sativa, Cucumis sativus, Sorghum bicolor, Bidens pilosa).
• Molecular docking studies to identify interactions with plant protein targets.

Main Results:

• Compound 16a demonstrated significant inhibition of sorghum growth (70% at 500 μm, 66% at 300 μm), exceeding the efficacy of S-metolachlor.
• All synthesized compounds exhibited either growth inhibition or stimulation effects on seeds compared to controls.
• Molecular docking revealed that compounds 15a, 15b, 17a, and 17b form complexes with mitogen-activated protein kinase (MAPK) 5R92.

Conclusions:

• The synthesized imides show promise as new agrochemicals, with some exhibiting superior or equivalent herbicidal activity to commercial standards.
• Mitogen-activated protein kinase is identified as a potential molecular target for these imide compounds.
• Further development of these imides could lead to effective solutions for weed management in agriculture.