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Additional file 1: of Novel prodrugs of decitabine with greater metabolic stability and less toxicity

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posted on 2019-08-02, 07:08 authored by Naoko Hattori, Magoichi Sako, Kana Kimura, Naoko Iida, Hideyuki Takeshima, Yoshitaka Nakata, Yutaka Kono, Toshikazu Ushijima
Table S1. Primers for qMSP and RT-qPCR. Figure S1. Screening of 35 synthesized compounds. (A) The DNA-demethylating activity of four 5′-O-trialkylsilylated AZAs and one 5′-O-trialkylsilylated DAC was screened under the drug treatment schedule on days 1 and 3. All 5′-O-trialkylsilylated AZAs exhibited a very low luciferase activity. (B) The DNA-demethylating activity of 11 5′-O-trialkylsilylated AZAs and 19 5′-O-trialkylsilylated DACs was screened under the drug treatment schedule on day 1. All 5′-O-trialkylsilylated AZAs displayed a considerably lower luciferase activity than that exhibited by DAC. Eleven 5′-O-trialkylsilylated DACs were selected for further study as their luminescence levels were at 1.0 × 106 cps or more using 1.0 μM concentration. AZA, azacitidine; cps, counts/photons per second; DAC, decitabine. Figure S2. Primer positions for methylation analysis of the marker region. Primers were designed to analyze the level of DNA demethylation of the exogenous UCHL1 promoter specifically. Since the reverse primer for the unmethylated DNA and the forward primer for the methylated DNA were located in the MetLuc sequence, we were able to distinguish between the exogenous and endogenous UCHL1 promoters. Figure S3. Blood counts and chemistry. No differences in the number of red blood cells and in the level of platelets, hemoglobin, hematocrit, aspartate aminotransferase (AST), and blood urea nitrogen (BUN) were observed among the groups treated with DAC, OR-2003, and OR-2100. Results are shown as mean ± SD (n = 5 or 6/group). DAC, decitabine; SD, standard deviation. (DOCX 1253 kb)

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