Hycanthone is a thioxanthenone derivative that acts as a DNA intercalator, inhibiting both RNA synthesis and DNA topoisomerases I and II. It disrupts nucleic acid biosynthesis and directly binds to apurinic endonuclease-1 (APE1) with a dissociation constant (KD) of 10 nM. Hycanthone is an active metabolite of Lucanthone, functioning as an anti-schistosomal agent[1].
体内研究
Studies demonstrate that adult sensitive worms experience a progressive decrease in the incorporation of tritiated thymidine into TCA-precipitable material following Hycanthone treatment. Conversely, immature worms are entirely unaffected at all times tested. Male worms treated with Hycanthone exhibit potential partial recovery from initially low levels of incorporation. Additionally, drug-sensitive worms treated with Hycanthone show a 40 to 50% reduction in the incorporation of tritiated leucine within the first four days post-treatment. Seven days after Hycanthone administration, both ribosomal RNA species in treated worms are diminished by at least 80% compared to untreated worms, hinting at a possible accumulation of heavier precursor molecules[2].
体外研究
The IC50 of Hycanthone for inhibiting APE1's ability to incise depurinated plasmid DNA is 80 nM[1].
When treated with Hycanthone (0.05-100 µM; for 2 h) in the presence of Cycloheximide (CHX), there is an enhanced cleavage of APE1, which is suppressed by 1% DMSO[1].
Hycanthone at a concentration of 20 mg/mL or higher increasingly affects cell viability. Observations indicate that escalating doses of Hycanthone, from 0.1 to 10 μg/mL, significantly reduce viral interferon production by up to 73% compared to controls[3].
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