Biol. Pharm. Bull. 28(4) 591—595 (2005)

cial problems affecting the skin and nails, to deeply invasive and disseminated infections, such as systemic candidiasis and pulmonary aspergillosis. These illnesses reduce the quality of life of patients and can progress to become life threatening. Four classes of antifungal drugs are available at present: polyene macrolides, azoles, flucytosine and candins. However, their use is restricted by their limited activity spectra, toxicity, hazardous interactions and non-optimal pharmacokinetics. Furthermore, reports of important fungal pathogens that are resistant to these drugs are becoming more frequent. The increasing incidence of fungal infections, combined with the reduced efficacy of the currently available drugs, highlights the need for new antifungal drugs with different modes of action and targets that are distinct from those traditionally used. Myristoyl-CoA:protein N-myristoyltransferase (Nmt; EC 2.1.3.97) catalyzes the transfer of the fatty acid, myristate (C14 : 0), from myristoyl-CoA to the amino (N)-terminal glycine residue of a number of eukaryotic cellular and viral proteins. Myristoylation is required for full expression of the biological function of these proteins, ensuring conformational stability and the ability to interact with membranes or the hydrophobic domains of other proteins. Nmt performs this critical function in the eukaryotic cell and is essential for the in vitro viability of many species of fungi, including Candida albicans and Cryptococcus neoformans, which are both medically important. Furthermore, C. albicans with defective Nmt loses the ability to infect mice. So far, studies aiming to create novel antifungal agents have described two classes of synthetic fungal Nmt inhibitors: the benzofurans and the benzothiazoles. The antifungal properties of the benzofurans have been well studied both in vitro and in vivo, but there is a paucity of information on the benzothiazoles. We performed in silico and wet screening of approximately 3000000 commercially available small compounds in our laboratory. We identified 20 compounds with C. albicans Nmt (CaNmt) inhibitory activity, and among these, two compounds had the benzothiazole scaffold. Based on our screening results and information on the structure–activity relationship, we have synthesized the novel benzothiazole derivative FTR1335 (Fig. 1). The present study examined the properties of FTR1335 with the aim of developing it further as an antifungal drug.