Abstract
Even though Candida spp. are staying commonly on human skin, it is also an opportunistic pathogenic fungus that can cause candidiasis. The emergence of resistant Candida strains and the toxicity of antifungal agents have encouraged the development of new classes of potent antifungal agents. Novel naphthalen-2-acyl imidazolium salts (NAIMSs), especially 1,4-dialkoxy-NAIMS from 1,4-dihydroxynaphthalene, were prepared and evaluated for antifungal activity. Those derivatives showed prominent anti-Candida activity with a minimum inhibitory concentration (MIC) of 3.125 to 6.26 μg/mL in 24 h based on microdilution antifungal susceptibility test. Among the tested compounds, NAIMS 7c showed strongest antifungal activity with 3.125 μg/mL MIC value compared with miconazole which showed 12.5 μg/mL MIC value against Candida spp., and more importantly >100 μg/mL MIC value against C. auris. The production of reactive oxygen species (ROS) was increased and JC-1 staining showed the loss of mitochondrial membrane potential in C. albicans by treatment with NAIMS 7c. The increased release of ultraviolet (UV) absorbing materials suggested that NAIMS 7c could cause cell busting. The expression of apoptosis-related genes was induced in C. albicans by NAIMS 7c treatment. Taken together, the synthetic NAIMSs are of high interest as novel antifungal agents given further in vivo examination.
Highlights
Infections by invasive fungal pathogens result from immunosuppression, long-term broad-spectrum antimicrobials, endocrinopathies, organ transplantation and use of indwelling catheters [1,2]
We tried to synthesize 2-acetyl-1,4-dialkoxynaphthalnes 4, a key intermediate to target naphthalen-2-acyl imidazolium salts (NAIMSs) 7 by direct alkylation of 1,4-dihydroxynaphthalene followed by Friedel–Crafts acylation
The compounds 2 were synthesized in high yield from 1,4-diacetoxynaphthalene
Summary
Infections by invasive fungal pathogens result from immunosuppression, long-term broad-spectrum antimicrobials, endocrinopathies, organ transplantation and use of indwelling catheters [1,2]. Candida spp. is a critical invasive fungal pathogen causing disease in humans, normally responsible for 90% of mucosal infections and 60% of candidiasis episodes [3]. Various compounds are currently used to control Candida infectious diseases, including well-known azoles such as fluconazole, miconazole and others, the mortality of patients with Candida infection is above 15% [4,5]. The drugs currently used against fungal pathogens have limitations because of their toxicity [6,7]. There is an urgent need for a new drug to treat Candida infection
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