Integrating Natural Product Chemistry Workflows into Medicinal Chemistry Laboratory Training: Building the PRISM Library and Cultivating Independent Research

Abstract

Chemical screening libraries often feature natural product extracts (NPEs) due to the intriguing biological activities they possess and the structural diversity found in their individual components. A research project originally designed to create an extract library of every specimen in the University of Rhode Island (URI) Heber W. Youngken Jr. Medicinal Garden soon turned into a laboratory-based teaching project in which upper-division undergraduate students generated and analyzed extracts in an academic minisemester project. Additionally, motivated upper-division undergraduates carried out independent research isolating biologically active molecules. Hands-on laboratory activities enhanced students’ knowledge of methodologies and workflows associated with extract analysis and biological evaluation of botanical extracts. The synergy of the laboratory course with the independent study contributed to workforce preparation and library generation.

Screening the PRISM library against Staphylococcus aureus reveals a sesquiterpene lactone from Liriodendron tulipifera with inhibitory activity

“…Medicinal Garden. 20 Briefly, plants were separated into aerial and underground portions, then further divided (twigs, leaves, etc.) for extraction in both aqueous and organic (methanol) solvents.…”

“…In 2019, we developed an extract library of aqueous and organic extracts of the aerial and root portions of specimens found in the garden. 20 This resource, the Principal Rhode Island Secondary Metabolite (PRISM) library with Herein, we identified the organic (methanol) extract of the tulip tree leaves (Liriodendron tulipera) as having growth inhibitory properties against S. aureus DMS 1104, an MSSA strain. Using bioassay-guided isolation, the bioactive constituent was identified as the sesquiterpene lactone, laurenobiolide.…”

“…In 2019, we developed an extract library of aqueous and organic extracts of the aerial and root portions of specimens found in the garden. 20 This resource, the Principal Rhode Island Secondary Metabolite (PRISM) library with 135 extracts at present was screened for antibiotic activity against MSSA.…”

“…Plant extracts in the PRISM library were prepared as previously described from specimens in the Heber W. Youngken Jr. Medicinal Garden 20. Briefly, plants were separated into aerial and underground portions, then further…”

Incorporating LC–MS/MS Analysis and the Dereplication of Natural Product Samples into an Upper-Division Undergraduate Laboratory Course

“…To accomplish this, a tandem mass spectrometry component was added to the existing framework of a minisemester classroom-based research project. 20 The recent acquisition of a Thermo Fisher Scientific LTQ XL mass spectrometer devoted to undergraduate student learning allowed for the creation of the experiment. Students analyzed botanical samples using LC−MS/MS and performed database analysis to dereplicate the samples.…”