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• W1991341187 abstract "The antifungal properties of 515 synthetic and semi-synthetic protoberberines were investigated. HWY-289 was chosen for further study because it exhibited the most significant anti-Candida activity (MICs were 1.56 mg/L for Candida albicans and Candida krusei; 6.25 mg/L for Candida guilliermondii) but did not demonstrate toxicity in rats. HWY-289 inhibited the incorporation of l-[methyl-14C]methionine into the C-24 of ergosterol in whole cells of C. albicans (IC50 20 μM). However, HWY-289 (100 μM) had no effect on mammalian cholesterol biosynthesis in rat microsomes while miconazole (100 μM) was a potent inhibitor of cholesterol biosynthesis under identical assay conditions. A second major target site for HWY-289 was identified that involves cell wall biosynthesis in C. albicans. HWY-289 was a potent inhibitor of the chitin synthase isozymes CaCHS1 and CaCHS2, with IC50 values of 22 μM for each enzyme. The effect was highly specific in that HWY-289 had no significant effect on C. albicans CaCHS3 (IC50 > 200 μM). Thus, HWY-289 compared favourably with well-established antifungal agents as an inhibitor of the growth of Candida species in vitro, and may have considerable potential as a new class of antifungal agent that lacks toxic side effects in the human host." @default.
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• W1991341187 date "2001-05-01" @default.
• W1991341187 modified "2023-09-27" @default.
• W1991341187 title "HWY-289, a novel semi-synthetic protoberberine derivative with multiple target sites in Candida albicans" @default.
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• W1991341187 doi "https://doi.org/10.1093/jac/47.5.513" @default.
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