Do Fukui function maxima relate to sites of metabolism? A critical case study.

The usefulness of local reactivity descriptors for understanding drug metabolism is investigated. Electrophilic Fukui functions are calculated for 18 drugs and 11 agrochemicals and their relation to experimentally observed metabolites is discussed. Maxima of the Fukui functions correspond to major sites of metabolic attack in many examples, facilitating a posteriori understanding of experimental findings.

Synthesis and anthelmintic activity of thioamide analogues of cyclic octadepsipeptides such as PF1022A.

The tetra- and mono-thionated cyclic octadepsipeptides represent novel cyclic octadepsipeptide derivatives with broad-spectrum activity against parasitic nematodes in mice and sheep. Some of these show better activity than the potent natural anthelmintic cyclic octadepsipeptide PF1022A against Hymenolepis nana, Heterakis spumosa and Trichinella spiralis larvae in mice. In particular, they show improved efficacy against Haemonchus contortus and Trichostrongylus colubriformis in sheep compared with PF1022A.

Novel small strongyle (Cyathostominae) beta-tubulin sequences.

Several coding sequences of the benzimidazole (BZ) target beta-tubulin have been described for different parasitic nematodes. However, until recently no tubulin sequences from Cyathostome species were available, despite the importance of BZ resistance in horses in the field. Here, we describe several full-length beta-tubulin coding sequences of two major small strongyle species, namely Cylicocyclus nassatus and Cyathostomum coronatum.