Exhaustive conformational searches for superimposition of acaricidal compounds

Three-dimensional common structural features among three acaricidal compounds which inhibit respiratory complex I were investigated, assuming that they have a similar binding mode. The techniques of COMPASS (COMmon geometrical Pattern Search System) and ''molecular field fitting'' were employed and exhaustive conformational space searches were performed without any presumption. The results suggested that the ''active conformations'' of these compounds are non-planar. Within each type a lone-pair containing functional group on the heterocyclic ring as well as a hydrophobic region with a t-butyl group overlapped well, despite the difference in size and chemical nature of the connecting bridge. Structure-activity relationships of the compounds are explained successfully by the energy of the ''active conformation''. The present study demonstrates the usefulness of the exhaustive conformational search to derive simultaneously the ''active conformation'' and the mode of superimposition.