A Fluorescence-based Protocol for Preliminary Screening of Protein Synthesis Inhibitors from Natural Sources

Natural products represent a rich source of therapeutic compounds with applications across multiple diseases, particularly cancer. By leveraging these biomolecules as structural templates in drug discovery, researchers have achieved both faster development timelines and improved biological effectiveness compared to fully synthetic compounds. The protein synthesis pathway has emerged as a compelling target for natural products, especially given its involvement in hard-to-treat cancers. The potent protein synthesis inhibitor cycloheximide, derived from Streptomyces griseus, exemplifies the potential of natural compounds in this space. As these natural product derivatives are developed into drug-like molecules, confirming their protein synthesis inhibitory activity remains a crucial validation step. The primary aim is to provide an undergraduate-friendly protocol for rapid evaluation of compound inhibition activity. The protocol employs a fluorescent substrate and advanced fluorescence microscopy techniques to systematically detect and measure the inhibitory capabilities of these natural products. The study examined compounds derived from two plant species: Pinus sylvestris and Psoralea corylifolia. Using cycloheximide as a reference inhibitor, both natural products showed varying levels of protein synthesis inhibition.