The Efficacy, Toxicity & Pharmacology of Dillapiole: a potential new treatment for Tularemia

Francisella tularensis, a highly infectious bacterium, is the causative agent of Tularemia (rabbit fever). Categorized by Center for Disease Control and Prevention as Category A bioterrorism agent, tularensis highest level concern. Previously, we identified that dillapiole, compound extracted from fennel, dampens F. virulence gene expression. While having no apparent effect on viability treatment with this leads to reduced bacterial during in vitro infection THP-1 monocytes RAW 264.7 macrophages. In study, sought determine if dillapiole exhibited therapeutic vivo, characterize toxicity pharmacology compound. murine tularemia model, female mice treated trended toward increased survival compared those vehicle. However, dillapiole- or vehicle-treated male showed mortality females, suggesting gender-specific differences immune response tularensis. Dillapiole was not toxic HEK-293 cells vitro, nor primary human hepatocytes when tested up concentration 11 mg/ml (50 mM). shown be relatively stable human, rat, mouse plasma half-life greater than 120 minutes all cases. moderately high binding proteins (86% 75% plasma). addition, while moderate clearance rat liver microsomes, microsomes clearance. Collectively, these data could explain minimal efficacy observed vivo. Therefore, future investigations should involve model potential novel tularemia.