Herbicides are small molecules that inhibit specific molecular target sites within plant biochemical pathways and/or physiological processes. Inhibition of these sites often has catastrophic consequences that are lethal to plants. The affinity of these compounds for their respective target sites makes them useful tools to study and dissect the intricacies of plant biochemical and physiological processes. For instance, elucidation of the photosynthetic electron transport chain was achieved in part by the use of herbicides, such as terbutryn and paraquat, which act on photosystem II and I, respectively, as physiological probes. Work stemming from the discovery of the binding site of PS II–inhibiting herbicides was ultimately awarded the Nobel Prize in 1988. Although not as prestigious as the seminal work on photosynthesis, our knowledge of many other plant processes expanded significantly through the ingenious use of inhibitors as molecular probes. Examples highlight the critical role played by herbicides in expanding our understanding of the fundamental aspects of the synthesis of porphyrins and the nonmevalonate pathway, the evolution of acetyl-coenzyme A carboxylase, cell wall physiology, the functions of microtubules and the cell cycle, the role 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.