Synthesis and Antifungal Activity of Perylene Bisimide Derivatives

Abstract

The frequency of opportunistic fungal infection has increased drastically, mainly in patients who are immunocompromised due to organ transplant, leukaemia or HIV infection. Candida albicans is responsible for most infections caused by fungi; however, the incidence of non-albicans species that are resistant, less susceptible or potentially resistant to currently antifungal drugs, such as Candida parapsilosis, Candida krusei, Candida tropicalis, appears to be increasing. Filamentous fungi infections are less frequent than Candida species infection, but are associated with high mortality rates. Despite the addition of new classes of antifungals, the number of currently available drugs for the treatment of fungal infections remains limited.Perylene derivatives are compounds used in a variety of industrial applications for decades, especially in the dye-sensitized solar cells, organic light-emitting diodes, and organic thin film transistors. Moreover, these compounds have shown some anticancer, antiviral, antidepressant, and antibacterial activities.In this study, we have synthesized several perylene bisimide derivatives and evaluated the antifungal activity against human pathogenic yeasts (Candida spp.) and filamentous fungi (Aspergillus spp., Fusarium spp., and Trichophyton spp.).Three compounds (2-4) from the nine compounds tested presented relevant activity. Compound 2 was active against Candida albicans, C. parapsilosis and C. tropicalis with minimum inhibitory concentrations (MIC90) values of 25.0, 22.0 and 14.0 µg/mL, respectively. Similarly, compound 3 was active against these three yeasts with MIC90 values of 7.0, 5.0 and 6.0 µg/mL, respectively, while compound 4 showed a MIC90 value below 3,1 µg/mL, being this compound the most potent. These three compopunds also showed activity against filamentous fungi, F. oxysporum, T. rubrum and T. mentagrophytes at a concentration of 50 µg/mL. The resultant data indicates that perylene bisimides (2-4) display wide spectrum and relevant antifungal activity. Compound 4 represents a new scaffold for the development of antifungal agents and warrant further structure activity relationship studies.