Herbicides are small molecules that inhibit specific molecular target siteswithin plant biochemical pathways and/or physiological processes. Inhibitionof these sites often has catastrophic consequences that are lethal toplants. The affinity of these compounds for their respective target sitesmakes them useful tools to study and dissect the intricacies of plantbiochemical and physiological processes. For instance, elucidation of thephotosynthetic electron transport chain was achieved in part by the use ofherbicides, such as terbutryn and paraquat, which act on photosystem II andI, respectively, as physiological probes. Work stemming from the discoveryof the binding site of PS II–inhibiting herbicides was ultimately awardedthe Nobel Prize in 1988. Although not as prestigious as the seminal work onphotosynthesis, our knowledge of many other plant processes expandedsignificantly through the ingenious use of inhibitors as molecular probes.Examples highlight the critical role played by herbicides in expanding ourunderstanding of the fundamental aspects of the synthesis of porphyrins andthe nonmevalonate pathway, the evolution of acetyl-coenzyme A carboxylase,cell wall physiology, the functions of microtubules and the cell cycle, therole of auxin and cyanide, the importance of subcellular protein targeting,and the development of selectable markers.

Antimicrobial resistance is a rapidly increasing problem impacting the successful treatment of bacterial infectious disease. To combat resistance, the development of new treatment options is required. Recent advances in technology have aided in the discovery of novel antibacterial agents, specifically through genome mining for novel natural product biosynthetic gene clusters and improved small molecule high-throughput screening methods. Novel targets such as lipopolysaccharide and fatty acid biosyntheses have been identified by essential gene studies, representing a shift from traditional antibiotic targets. Finally, inhibiting non-essential genes with small molecules is being explored as a method for rescuing the activity of ‘old’ antibiotics, providing a novel synergistic approach to antimicrobial discovery.

High throughput technologies continue to develop in response to the challenges set by the genome projects. This article discusses how the techniques of both high throughput screening (HTS) and synthesis can influence research in parasitology. Examples of the use of targeted and phenotype-based HTS using unbiased compound collections are provided. The important issue of identifying the protein target(s) of bioactive compounds is discussed from the synthetic chemist's perspective. This article concludes by reviewing recent examples of successful target identification studies in parasitology.