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- W2329712894 abstract "Miltefosine is an alkylphosphocholine that shows broad-spectrum in vitro antifungal activities and limited in vivo efficacy in mouse models of cryptococcosis. To further explore the potential of this class of compounds for the treatment of systemic mycoses, nine analogs (3a-3i) were synthesized by modifying the choline structural moiety and the alkyl chain length of miltefosine. In vitro testing of these compounds against the opportunistic fungal pathogens Candida albicans, Candida glabrata, Candida krusei, Aspergillus fumigatus, and Cryptococcus neoformans revealed that 2-(benzyldimethylammonio)ethyl hexadecyl phosphate (3a), 2-(dimethyl(4-nitrobenzyl)ammonio)ethyl hexadecyl phosphate (3d), and 2-(dimethyl(4-methoxybenzyl)ammonio) ethyl hexadecyl phosphate (3e) exhibited minimum inhibitory concentrations (MIC) of 2.5-5.0 µg/mL against all tested pathogens, when compared to miltefosine with MICs of 2.5-3.3 µg/mL. Compound 3a showed low in vitro cytotoxicities against three mammalian cell lines similar to miltefosine. In vivo testing of 3a and miltefosine against C. albicans in a mouse model of systemic infection did not demonstrate efficacy. The results of this study again raise concerns for this class of compounds as drug candidates for systemic mycoses including candidiasis." @default.
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- W2329712894 date "2013-07-04" @default.
- W2329712894 modified "2023-09-26" @default.
- W2329712894 title "Synthesis and Antifungal Activities of Miltefosine Analogs" @default.
- W2329712894 doi "https://doi.org/10.1055/s-0033-1348564" @default.
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