An Inquiry‐based Exercise in Medicinal Chemistry: synthesis of a molecular library and screening for potential anti‐malarial 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 multi‐step synthesis of a novel compound with anti‐inflammatory and/or anti‐malarial 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 CURE survey, suggest that students participating in both classes had higher gains than the average student. Support or Funding Information Monetary support for this project came from the Excellence in Science Fund of Lawrence University, NIH grant R15 AI065505‐01A1, and NSF grants 0521112 and CHE‐0923473, and the Sherman Fairchild Foundation.