Synthesis of Chimeric Thiazolo‐Nootkatone Derivatives as Potent Antimicrobial Agents

• DOI: 10.1002/cmdc.202100230
• Publication Date: 2021-05-06T21:12:31Z
• Authors: Ibrahim S. Alkhai...; Hansa Raj K. C.; Rawan Alnufaie; David Gilmore; Mohammad A. Alam
• Keywords: Polycyclic Sesquiterpenes; 0301 basic medicine; Staphylococcus aureus; Dose-Response Relationship, Drug; Enterococcus faecium; Molecular Conformation; Microbial Sensitivity Tests; Anti-Bacterial Agents; 3. Good health; Structure-Activity Relationship; Thiazoles; 03 medical and health sciences; Humans

AbstractNootkatone, an approved insecticide, is a well‐known natural product from grapefruit. A series of fused‐thiazole derivatives of nootkatone have been synthesized, and these new compounds were tested against several strains of bacteria. Some of these compounds are found to be potent antimicrobial agents against Staphylococcus aureus and Enterococcus faecium with minimum inhibitory concentration (MIC) values as low as 1.56 μg/mL. The lead compound is bactericidal and very potent against S. aureus persisters. These compounds are nontoxic to human cancer cell lines at 10 μm concentration.