The discovery of aspirin represents one of the most important achievements in the history of medicinal chemistry. First synthesized in 1897 from salicylic acid, a bioactive molecule found in willow bark, aspirin had immediate therapeutic success as the world’s first mass produced analgesic drug. More than 100 years after its initial synthesis, aspirin remains one of the most highly researched drugs in the world with up to 1,000 aspirin-related clinical trials conducted each year. In addition to its use as an analgesic, aspirin is frequently used for its anti-inflammatory, anti-pyretic, and anti-coagulant properties. Recent research has also shown that aspirin has promising anticancer and antibacterial activities. Based on aspirin’s plethora of medicinal activities, the modification of this scaffold was of interest in the search for new bioactive molecules. In this study, a library of structurally diverse aspirin analogs with varying degrees of hydrophobicity and different electronic characteristics was synthesized via a multi-year course-based research experience in an Organic Chemistry 2 Lab class at Lawrence Technological University. Using various acyl chlorides, a homologous series of acyl groups ranging from three to nine carbons were attached to the salicylic acid scaffold. More sterically hindered analogs were also prepared using additional structurally diverse acyl chlorides. Following purification via C18 reversed-phase chromatography and characterization via high-resolution NMR spectroscopy, the antibacterial activity of aspirin analogs was evaluated using both Gram-positive and Gram-negative bacterial strains. Preliminary results suggest that longer alkyl chains may confer selectivity against Gram-positive bacteria. Anticancer assay results will also be discussed. Future studies will focus on diversifying the aromatic ring of the salicylic acid scaffold.

Synthesis and medicinal activity of structurally diverse aspirin analogs

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.