PROSPECTS FOR RATIONAL APPROACHES TO ANTHELMINTIC DISCOVERY

Rational approaches to anthelmintic discovery include the design of sc reens for compounds directed at specific proteins in helminths that ar e pharmacologically distinguishable from their vertebrate homologues. The existence of several anthelmintics that selectively target the neu romusculature of helminths (e.g. levamisole, ivermectin, praziquantel, metrifonate), together with recent basic research in helminth physiol ogy, have contributed to the recognition that neurobiology distinguish es these organisms from their vertebrate hosts. In this survey, we foc us on mechanism-based screening and its application to anthelmintic di scovery, with particular emphasis on targets in the neuromusculature o f helminths. Few of these proteins have been exploited in chemotherapy . However, recent studies in comparative pharmacology and molecular bi ology, including the C. elegans genome project, have provided insights on potential new targets and, in some cases, molecular probes useful for their incorporation in mechanism-based screens.