Screening a Natural Product-Inspired Library for Anti-Phytophthora Activities

Phytophthora is a genus of microorganisms that cause devastating dieback and root-rot diseases in thousands of plant hosts worldwide. The economic impact of Phytophthora diseases on crops and native ecosystems is estimated to be billions of dollars per annum. These invasive pathogens are extremely difficult to control using existing chemical means, and the effectiveness of the few treatments available is being jeopardized by increasing rates of resistance. There is an urgent need to identify new chemical treatments that are effective against Phytophthora diseases. Natural products have long been regarded as "Nature's medicine chest", providing invaluable leads for developing front-line drugs and agrochemical agents. Here, we have screened a natural product-inspired library of 328 chemicals against two key Phytophthora species: Phytophthora cinnamomi and Phytophthora agathidicida. The library was initially screened for inhibition of zoospore germination. From these screens, we identified twenty-one hits that inhibited germination of one or both species. These hits were further tested in mycelial growth inhibition studies to determine their half-maximal inhibitory concentrations (IC₅₀s). Four compounds had IC₅₀ values of approximately 10 µM or less, and our best hit had IC₅₀s of approximately 3 µM against both Phytophthora species tested. Overall, these hits may serve as promising leads for the development of new anti-Phytophthora agrochemicals.