RESUMO
BACKGROUND: Radulanin A is a natural 2,5-dihydrobenzoxepin synthesized by several liverworts of the Radula genus. Breakthroughs in the total synthesis of radulanin A paved the way for the discovery of its phytotoxic activity. Nevertheless, its mode-of-action (MoA) has remained unknown so far and thus was investigated, in Arabidopsis thaliana. RESULTS: Radulanin A phytotoxicity was associated with cell death and partially depended on light exposure. Photosynthesis measurements based on chlorophyll-a fluorescence evidenced that radulanin A and a Radula chromene inhibited photosynthetic electron transport with IC50 of 95 and 100 µm, respectively. We established a strong correlation between inhibition of photosynthesis and phytotoxicity for a range of radulanin A analogs. Based on these data, we also determined that radulanin A phytotoxicity was abolished when the hydroxyl group was modified, and was modulated by the presence of the heterocycle and its aliphatic chain. Thermoluminescence studies highlighted that radulanin A targeted the QB site of the Photosystem II (PSII) with a similar MoA as 3-(3,4-dichloropheny)-1,1-dimethylurea (DCMU). CONCLUSION: We establish that radulanin A targets PSII, expanding QB sites inhibitors to bibenzyl compounds. The identification of an easy-to-synthesize analog of radulanin A with similar MoA and efficiency might be useful for future herbicide development. © 2023 Society of Chemical Industry.