An inquiry‐based exercise in medicinal chemistry: Synthesis of a molecular library and screening for potential antimalarial and anti‐inflammatory compounds

: The development of new medicines holds particular fascination for chemistry, biochemistry, and biology students interested in a career in medicine or the life sciences. The identification and refinement of lead compounds to treat diseases requires researchers to be facile in a number of different disciplines including organic synthesis, biochemistry, cell biology, and molecular biology. We have developed an interdisciplinary, inquiry-based laboratory spanning both organic chemistry and biochemistry classes that acquaints students with research in medicinal chemistry. The first part of the exercise takes place in the second semester of organic chemistry, where pairs of students design and execute their own multistep synthesis of a novel compound with anti-inflammatory and/or antimalarial potential. Later, in first semester biochemistry, many of the same students then test these synthesized compounds for cytotoxicity, inhibition of the enzyme nitric oxide synthase, and inhibition of the transcription factor NF-kB. Learning outcomes, measured by the Classroom Undergraduate Research Experience (CURE) survey, suggest that students participating in both classes had higher gains than an average student. © 2018 International Union of Biochemistry and Molecular Biology, 46(5):424-434, 2018.