Design, Synthesis, and Structure–Activity Relationship Studies of Magnolol Derivatives as Antifungal Agents

Abstract

Plant pathogenic fungi seriously affect agricultural production and are difficult to control. The discovery of new leads based on natural products is an important way to innovate fungicides. In this study, 30 natural-product-based magnolol derivatives were synthesized and characterized on the basis of NMR and mass spectroscopy. Bioactivity tests on phytopathogenic fungi (<i>Rhizoctonia solani</i>, <i>Fusarium graminearum</i>, <i>Botrytis cinerea</i>, and <i>Sclerotinia sclerotiorum</i>) in vitro of these compounds were performed systematically. The results showed that 11 compounds were active against four kinds of phytopathogenic fungi with EC₅₀ values in the range of 1.40-20.00 μg/mL, especially compound <b>L5</b> that exhibited excellent antifungal properties against <i>B. cinerea</i> with an EC₅₀ value of 2.86 μg/mL, approximately 2.8-fold more potent than magnolol (EC₅₀ = 8.13 μg/mL). Moreover, compound <b>L6</b> showed the highest antifungal activity against <i>F. graminearum</i> and <i>Rhophitulus solani</i> with EC₅₀ values of 4.39 and 1.40 μg/mL, respectively, and compound <b>L7</b> showed good antifungal activity against <i>S. sclerotiorum</i>. Then, an in vivo experiment of compound <b>L5</b> against <i>B. cinerea</i> was further investigated in vivo using infected tomatoes (curative effect, 50/200 and 36%/100 μg/mL). The physiological and biochemical studies illustrated that the primary action mechanism of compound <b>L5</b> on <i>B. cinerea</i> might change the mycelium morphology, increase cell membrane permeability, and destroy the function of mitochondria. Furthermore, structure-activity relationship (SAR) studies revealed that hydroxyl groups play a key role in antifungal activity. To sum up, this study provides a reference for understanding the application of magnolol-based antifungal agents in crop protection.