Nematicide Chalcones Act Synergistically on Caenorhabditis elegans and Meloidogyne incognita Without Disrupting Soil Microbial Diversity and with Limited Toxicity to Human Cells

Plant Parasitic Nematodes (PPNs), such as <i>Meloidogyne incognita</i>, cause significant agricultural losses worldwide. Conventional nematicides like methyl bromide are being phased out due to environmental and health concerns, prompting the search for safer alternatives. In previous studies, chalcones <b>17</b>, <b>25</b>, and <b>30</b>, flavonoid compounds, were shown to effectively kill the model nematode <i>Caenorhabditis elegans</i> at concentrations of 10^-4 M. However, the potential of these chalcones to act synergistically at lower concentrations has not been explored. In this study, the nematicidal efficacy of chalcones <b>17</b>, <b>25</b>, and <b>30</b> was evaluated individually and in combination at concentrations as low as 10^-6 M. The results demonstrate a strong synergistic effect, with combinations achieving 90-100% mortality in <i>C. elegans</i> within 3 days. Additionally, the combination index method revealed significant toxic effects against <i>M. incognita</i> with chalcones <b>17</b> and <b>30</b> in binary and ternary combinations. To assess the effects of these chalcones on nontarget organisms, chalcones were also tested for antimicrobial activity against soil bacteria; analysis of soil microbiota using 16S rRNA sequencing indicated that chalcones did not significantly disrupt microbial populations. Furthermore, tests on human pluripotent stem cells (hPSCs) reveal no major effects on the viability of these cells at concentrations as high as the concentrations needed to kill nematodes. These findings highlight the potential of chalcones <b>17</b>, <b>25</b>, and <b>30</b> for effective nematode control without harming soil bacteria or human cells.