Comparison of inhibition of polymerisation of mammalian tubulin and helminth ovicidal activity by benzimidazole carbamates.

The correlation between the inhibition of hatching of Haemonchus contortus eggs and inhibition of mammalian tubulin polymerisation by benzimidazole carbamates has been investigated. The hatching process was observed to be independent of the biomass (eggs plus debris) over a 6-fold range and the early (E1-E3) stages of egg development, but was dependent on the concentration of co-solvent (DMSO) and time of incubation. Benzimidazole carbamates with strong inhibitory activity against mammalian tubulin were potent inhibitors of egg hatch, while non-inhibitors failed to prevent hatching. It is postulated that the primary mode of action of these drugs on nematode eggs is the inhibition of microtubule-dependent processes within the developing egg. The implications and limitations of this correlation are discussed.