9-Deazaguanine is a purine nucleoside analog with oral activity, functioning as a potent inhibitor of purine nucleoside phosphorylase (PNP)[1-2]. 9-Deazaguanine inhibits DNA and RNA replication by competitively inhibiting the incorporation of guanine into nucleic acid structures and interfering with the binding of guanine to proteins[3-4].
In vitro, 9-Deazaguanine and difluoromethylene phosphonic acid analogs (DFPP-DG, 9-13) (0.1–100μM) were used to treat human lymphocytes, B-cell and T-cell leukemia, and lymphoma cell lines for 72 hours. 9-Deazaguanine showed mild inhibitory activity on cell proliferation[5].
In vivo, 9-Deazaguanine (67µmoles/kg) was administered as a single intravenous injection to anesthetized Sprague-Dawley rats. 9-Deazaguanine significantly increased urine volume, sodium excretion, and glucose excretion in the rats[6].
References:
[1] Wielgus-Kutrowska B, Breer K, Hashimoto M, et al. Trimeric purine nucleoside phosphorylase: exploring postulated one-third-of-the-sites binding in the transition state. Bioorg Med Chem. 2012 Nov 15;20(22):6758-69.
[2] V T Minnow Y, Suthagar K, Clinch K, et al. Inhibition and Mechanism of Plasmodium falciparum Hypoxanthine-Guanine-Xanthine Phosphoribosyltransferase. ACS Chem Biol. 2022 Dec 16;17(12):3407-3419.
[3] Abu El Asrar R, Margamuljana L, Abramov M, et al. Enzymatic Incorporation of Modified Purine Nucleotides in DNA. Chembiochem. 2017 Dec 14;18(24):2408-2415.
[4] Tian G, Katchur SR, Jiang Y, et al. Small molecule-mediated allosteric activation of the base excision repair enzyme 8-oxoguanine DNA glycosylase and its impact on mitochondrial function. Sci Rep. 2022 Aug 29;12(1):14685.
[5] Glavas-Obrovac L, Suver M, Hikishima S, et al. Antiproliferative activity of purine nucleoside phosphorylase multisubstrate analogue inhibitors containing difluoromethylene phosphonic acid against leukaemia and lymphoma cells. Chem Biol Drug Des. 2010 Apr;75(4):392-9.
[6] Jackson EK, Mi Z, Kleyman TR, et al. 8-Aminoguanine Induces Diuresis, Natriuresis, and Glucosuria by Inhibiting Purine Nucleoside Phosphorylase and Reduces Potassium Excretion by Inhibiting Rac1. J Am Heart Assoc. 2018 Nov 6;7(21):e010085.
9-Deazaguanine是一种嘌呤核苷类似物，具有口服活性，作为嘌呤核苷磷酸化酶(PNP)的强效抑制剂[1-2]。9-Deazaguanine 可通过竞争性抑制鸟嘌呤掺入核酸结构并干扰鸟嘌呤与蛋白质的结合，从而抑制DNA和RNA的复制[3-4]。
在体外，9-Deazaguanine及二氟亚甲基膦酸类似物(DFPP-DG, 9-13)(0.1–100μM)处理人淋巴细胞、B细胞和T细胞白血病及淋巴瘤细胞系72小时，9-Deazaguanine细胞增殖显示出轻微的抑制活性[5]。
在体内，9-Deazaguanine(67µmoles/kg)单次静脉注射，用于处理麻醉状态下的Sprague-Dawley大鼠。9-Deazaguanine显著增加了小鼠的尿量、尿钠排泄和尿葡萄糖排泄[6]。