Synthesis of aglycones, structure-activity relationships, and mode of action of lycosides as inhibitors of the asexual reproduction of Phytophthora.

Phytophthora are plant pathogens that damage agricultural products. Lycosides (1a-d), found in vegetable juice, have the potential to curb the rapid outbreak and crop damage caused by the asexual reproduction of Phytophthora. Here, aglycones 2a, b with slightly higher activity than lycosides were synthesized as a diastereomeric mixture (mix-2) possessing activity (IC50 = 4.1 µm) comparable with that of lycosides. The importance of the cyclohexanone structure and side-chain length was demonstrated via structure-activity relationship analysis using synthetic intermediates. In addition, the action mechanism of lycosides was investigated using transcriptome analysis, which revealed a contribution to proline biosynthesis inhibition, a process crucial for the asexual reproduction of Phytophthora. These findings indicate that lycosides (and aglycone) are environmentally benign agents that can be used for protecting agricultural products from Phytophthora pathogens.

Inhibitors of Asexual Reproduction of the Plant Pathogen Phytophthora from Tomato Juice: Structure-Activity Relationships and Transcriptome Analysis.

Phytophthora is a genus of fungus-like microorganisms that damages important crops, such as potatoes and tomatoes. Its asexual reproduction, which results in the production of numerous motile zoospores, is the cause of quick and severe outbreaks and crop damage. The search for substances that selectively inhibit the asexual reproduction of Phytophthora led to the isolation of the known natural products naringenin and flazin from tomato juice. They inhibit the sporangia formation of Phytophthora capsici at IC50 values of 8.8 and 7.2 µM. The study of the structure-activity relationship of 11 flavonoids, including naringenin, demonstrated that genistein was the most active (IC50 = 4.6 µM) and flavonols/flavanonols possessing the 3-hydroxy function showed little activity (IC50 = from 100 to >1000 µM). To demonstrate the mechanism of asexual reproduction inhibition by genistein, transcriptome analysis was carried out, which revealed the downregulation of some genes related to cell differentiation. The results suggest that certain flavonoids are environmentally benign agents that could be used to protect agricultural products from Phytophthora pathogens.