Drug Discovery: A Chemist’s Approach

Abstract

The medicinal chemist’s role in the multidisciplinary team involved in the modern day drug discovery process is to furnish agents for biochemical and biological experimentation and ultimately for therapeutic or prophylactic use in disease. In the antifungal area, the complexity of drug-fungal interactions and the intensity of the drug effect depend to a large extent on the concentration of drug in the active biophase (e.g. cell membrane), whereas the duration of the effect is determined by its persistence in a sufficient concentration at the active site. Drug molecules, therefore, owe much of their effect to interaction with biological structures, e.g. lipoprotein receptors, biomembranes and nucleic acids. This interaction triggers a series of steps, ultimately resulting in a macroscopic physiological change that constitutes the pharmacological effect. Ideally, only by first unravelling the relatively simple primary interaction between the drug molecule and a macromolecular structure can drug activity at the molecular level be understood. The increasing complexity of the whole organism, and then the animal model, requires an understanding of many more parameters — including some not always available to the chemist in the early phase of the programme.