Growth-Inhibitory Activity of a Clerodane Diterpene from Callicarpa americana Leaf Extracts and Its Derivatives against Cutibacterium acnes.

Cutibacterium acnes is a Gram-positive bacterium implicated in acne vulgaris, a common inflammatory skin disease. Rising antibiotic resistance in C. acnes highlights the need for new therapeutic agents. Callicarpa americana L., a shrub native to the southeastern United States, has a history of use in Native American traditional medicine. Bioassay-guided fractionation of C. americana leaf extracts led to the isolation of 12(S),16ξ-dihydroxycleroda-3,13-dien-15,16-olide (compound 1), a clerodane diterpene. Compound 1 exhibited growth-inhibitory activity against C. acnes (MIC: 8 μg/mL). A route to full synthesis of compound 1 and its derivatives was previously achieved by our groups, and we demonstrate that the growth inhibitory activities of synthetic compound 1 is equivalent to that of 1 isolated from C. americana. Furthermore, analogs of 1 were evaluated against C. acnes, with two structurally similar compounds demonstrating slightly reduced efficacy, supporting previous findings that the C-12 substituent, but not its stereochemistry, is important to the compound's activity. These findings expand knowledge of the antimicrobial properties of compound 1, provide the first report of any clerodane diterpene compound with activity against C. acnes, and serve as an important example of the role of how plant natural products can aid the drug discovery pipeline.