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Invasive fungal infections are increasing worldwide due to an expanding number of immunocompromised patients as well as an increase in drug-resistant fungi. While fungal resistance has increased, this resistance has not been accompanied by the development of new antifungals. A common class of antifungal agents that are prescribed are the azoles, which contain either a triazole or an imidazole group. Unfortunately, current azoles, like fluconazole, have been shown to be less effective with the increase in resistant fungal pathogens. Therefore, the development of novel azole antifungal compounds is of urgent need. The objective of this research was to synthesize triazole-containing small molecules with potent antifungal activity. The scaffold of the synthesized compounds contains a triazole moiety and was synthesized via a copper-catalyzed azide-alkyne click reaction (CuAAC) between the appropriate alkyne and azide intermediates. The minimum inhibitory concentrations of these compounds were determined using standard broth microdilution assays against opportunistic bacteria and fungi associated with life-threatening invasive fungal infections. Although the synthesized compounds possessed no antimicrobial activity, these results can be used to further the long-term goal of developing and optimizing lead compounds with potentin vitroantifungal activity. 

Polycyclic aromatic hydrocarbons are ubiquitous air pollutants, with additional widespread exposure in the diet. PAH exposure has been linked to adverse birth outcomes and long-term neurological consequences. To understand genetic differences that could affect susceptibility following developmental exposure to polycyclic aromatic hydrocarbons, we exposed mice with variations in the aryl hydrocarbon receptor and the three CYP1 enzymes from gestational day 10 (G10) to weaning at postnatal day 25 (P25). We found unexpectedly high neonatal lethality in high-affinity AhrbCyp1b1(-/-) knockout mice compared with all other genotypes. Over 60% of BaP-exposed pups died within their first 5 days of life. There was a significant effect of BaP on growth rates in surviving pups, with lower weights observed from P7 to P21. Again, AhrbCyp1b1(-/-) knockout mice were the most susceptible to growth retardation. Independent of treatment, this line of mice also had impaired development of the surface righting reflex. We used high-resolution mass spectrometry to measure BaP and metabolites in tissues from both dams and pups. We found the highest BaP levels in adipose from poor-affinity AhrdCyp1a2(-/-) dams and identified three major BaP metabolites (BaP-7-OH, BaP-9-OH, and BaP-4,5-diol), but our measurements were limited to a single time point. Future work is needed to understand BaP pharmacokinetics in the contexts of gestation and lactation and how differential metabolism leads to adverse developmental outcomes.