Tulipaline A: Structure-activity aspects as a nematicide and V-ATPase inhibitor

Carbonyl groups are known to form covalent adducts with endogenous proteins, but so far, their nematicidal mechanism of action of has been overlooked. The nematicidal activity of ten lactones was tested in vitro against the root knot nematodes Meloidogyne incognita and Meloidogyne arenaria. In particular, the saturated lactones alpha-methylene-gamma-butyrolactone or tulipaline A (1) and gamma-butyrolactone (3) were active against M. incognita with an EC50/48h of 19.3 +/- 10.0 and 40.0 +/- 16.2 mg/L respectively. Moreover the alpha, beta-unsaturated lactone 5,6-dihydro-2H-pyran-2-one (2) exhibited the strongest nematicidal activity against the two species with EC50/48h 14.5 +/- 5.3 and 21.2 +/- 9.7 mg/L respectively. Here we propose that the toxic effects of lactones and aldehydes on M. incognita and M. arenaria might be a consequence of their vacuolar-type H+-ATPase (V-ATPase) inhibition activity; in fact alpha-methylene-gamma-butyrolactone (1) and salicylaldehyde (12) produced an increased pH in lysosomal-like organelles on HeLa human cell line and this alteration was most likely related to a V-ATPase impairment