Allylic Selenocyanates as New Agents to Combat Fusarium Species Involved with Human Infections

Fusarium is an emerging opportunistic fungal pathogen that causes local or systemic infections. The successful use of a therapeutic drug or combination antifungal therapies against Fusarium spp. are compromised because reports of multidrug resistance are currently frequent. Thus, the development of new antifungal capable of combating multidrug‐resistant Fusarium strains becomes necessary. This study presents the synthesis of seven new allylic selenocyanates and their screening against Fusarium spp. Minimum inhibitory concentrations (MICs) of these compounds ranged from 4 to 64 μg mL−1, with the mechanism of action being related to fungal cell membrane disruption. Specific structural changes, such as widespread thinning along the hyphae, were observed by scanning electron microscopy. The effect of selenocyanates on cell viability and genotoxicity are concentration dependent, however they did not cause mutagenicity in human cells. Five selenocyanates were identified as nonirritant by the ex‐vivo HET‐CAM (Hen′s Egg Test‐Chorioallantoic Membrane) method. Allylic selenocyanates represents a promising alternative in the treatment and prevention of fusariosis. This study provides a library of seven allylic selenocyanates with minimum inhibitory concentrations (MICs) up to 4 μg mL−1 against multidrug resistant Fusarium spp., an opportunistic fungal that causes serious human infections. The mechanism of action of selenocyanates is related to fungal cell membrane disruption, through complexation with ergosterol. The toxicity was concentration dependent, but the compounds tested were neither human leukocyte mutagenic nor irritant to the chorioallantoic membrane. Then, selenocyanates represents a promising alternative in the treatment of fusariosis.