Antifungal activity of novel compound EIPE-1 against Cryptococcus neoformans

Abstract

Cryptococcus neoformans is an opportunistic fungal pathogen of the respiratory tract, which is responsible for over 200,000 deaths annually. Antifungal drugs have been used to treat fungal infections for many decades; however, due to similarities between fungal and mammalian cells, these drugs are often toxic. In these last few decades, the fungi have also become resistant to the antifungal drugs. EIPE-1 was synthesized from vanillin, and was shown to have activity against methicillin resistant S. aureus (MRSA), and other gram-positive bacterial pathogens. We hypothesized that EIPE-1 could be used to kill fungal pathogens. For this study, we tested EIPE-1 against C. neoformans using a minimum inhibitory concentration (MIC) assay and an in vitro model of intracellular macrophage growth using RAW macrophages. EIPE-1 has antifungal activity in our MIC assay, with an MIC value of 1.749 ug/ml. In addition, after incubation of C. neoformans with RAW macrophages and EIPE-1, treatment with EIPE-1 had significant antifungal effects on C. neoformans compared to C. neoformans alone and compared to C. neoformans with RAW macrophages. In further studies, we will examine the mechanism of EIPE-1 anti-fungal activity, and we will also test EIPE-1 against other fungal pathogens including Candida albicans.