In vitro nematicidal activity of aryl hydrazones and comparative GC-MS metabolomics analysis

A series of aryl hydrazones were synthesized and in vitro assayed for their activity on the root-knot nematode Meloidogyne incognita. The phenylhydrazones of thiophene-2-carboxyaldehyde 5, 3-methyl-2-thiophenecarboxyaldehyde 6 and salicylaldehyde 2, were the most potent with EC50/48h values of 16.6 ± 2.2, 23.2 ± 2.7, and 24.3 ± 1.4 mg/L, respectively. A GC-MS metabolomics analysis, after in vitro nematode treatment with hydrazone 6 at 100 mg/L for 12 h, revealed elevated levels of fatty acids such as lauric acid, stearic acid, 2-octenoic acid and palmitic acid. While control samples showed highest levels of monoacylglycerols such us monostearin and 2-monostearin. Surprisingly, after 2h treatment with hydrazone 6, nematodes excreted three times the levels of ammonia eliminated in the same conditions by controls. Thus, phenylhydrazones may represent a good scaffold in the discovery and synthesis of new nematicidal compounds while a metabolomics approach may be helpful in understanding their mechanisms of toxicity and mode of action.