Epoxy tetrahydrophthalimides as potential bioactive agents: synthesis and computational study

Due to the growing resistance of weeds to known herbicides, the search for new bioactive substances has been increasing in recent years. Imides belong to an important class of chemical compounds known to present various biological activities such as herbicide, fungicide, insecticide, and bactericide. In this study, the synthesis, purification, structural elucidation, and bioassays of four pairs of epoxy tetrahydrophthalimides 15a-18a and 15b-18b were conducted. Additionally in silico studies were performed to identify potential biological targets for the synthesized compounds.

The target compounds were prepared using a four-step synthetic route that starts with a microwave-assisted Diels-Alder reaction between maleic anhydride and isoprene. All synthesized compounds had their phytotoxicity evaluated using germination tests in Petri dishes against Lactuca sativa, Cucumis sativus, Sorghum bicolor and Bidens pilosa. At concentrations of 500 and 300 μm substance 16a presented inhibition of 70% and 66%, respectively, of the aerial parts of sorghum plants, which is higher than that observed for the commercial herbicide S-metolachlor. Molecular docking studies were performed for compounds 15a, 15b, 17a, and 17b, indicating that they form complexes with the mitogen-activated protein kinase 5R92, which shares similar amino acid sequences with those found in plants.

All substances caused inhibition or stimulation of seed growth compared to the control. Some substances caused plant growth inhibition superior or equivalent to the commercial herbicide, denoting these imides for the development of new agrochemicals. In silico studies suggest that mitogen-activated protein kinase may be the target of these compounds. © 2025 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.