Honokiol, a natural product isolated from the bark of magnolia trees, has been used for centuries in traditional eastern medicine as a therapeutic bactericide. Previous work has explored the use of honokiol-inspired analogs for the treatment of oral bacteria and biofilms, leading to the identification of CRO 215. This work explores the structure-activity relationship (SAR) of CRO 215 and other honokiol-inspired analogs for use as topical antibiotics. The minimum inhibitory concentration (MIC) of these compounds was determined for a variety of Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii (See Table 1). While CRO 215 was very active against Gram-positive bacteria, it failed to target Gram-negative bacteria and the HD20 (the concentration at which 20% of mammalian red blood cells are hemolyzed) indicated that this compound was toxic at low concentrations. Modifications to the substituents ortho to the phenol yielded CRO 263, a broad spectrum antibacterial with lower toxicity. Unfortunately, this modification led to a marked decrease in potency. Modification of the two-carbon linker of CRO 215 yielded HFR 115, a less toxic compound with activity similar to CRO 215 against Gram-positive bacteria. Presently, further modifications to the scaffold are underway to identify a more potent broad-spectrum antibacterial, and experiments are being undertaken to determine the bactericidal mechanism of action.

Honokiol-inspired analogs as topical antibiotics

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

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