: Multiple drug resistant fungi pose a serious threat to human health, therefore the development of completely new antimycotics is of paramount importance. The in vitro antifungal activity of the original, 1-amino-5-isocyanonaphthalenes (ICANs) was evaluated against reference strains of clinically important Candida species. Structure-activity studies revealed that the naphthalene core and the isocyano- together with the amino moieties are all necessary to exert antifungal activity. 1,1-N-dimethylamino-5-isocyanonaphthalene (DIMICAN), the most promising candidate, was tested further in vitro against clinical isolates of Candida species, yielding a minimum inhibitory concentration (MIC) of 0.04-1.25 µg/mL. DIMICAN was found to be effective against intrinsically fluconazole resistant Candida krusei isolates, too. In vivo experiments were performed in a severly neutropenic murine model inoculated with a clinical strain of Candida albicans. Daily administration of 5 mg/kg DIMICAN intraperitoneally resulted in 80% survival even at day 13, whereas 100% of the control group died within six days. Based on these results, ICANs may become an effective clinical lead compound family against fungal pathogens.
Keywords: 1,1-N-dimethylamino-5-isocyanonaphthalene; 1-amino-5-isocyanonaphthalenes; C. albicans; Candida species; antifungal effect; multiple drug resistance.