Zidovudine is a synthetic nucleoside analog that blocks replication of the human immunodeficiency virus (HIV) by inhibiting reverse transcriptase[1]. Zidovudine has been used as a model compound to develop a series of related derivatives for viral inhibition studies[2].
In vitro, Zidovudine treatment for 48 hours significantly inhibited HIV-1 activity in primary human fetal astrocytes (PFA) with an EC50 value of 1.311±0.130µM[3]. Treatment with 500μM Zidovudine for 24h induced upregulation of cyclin D1 in HeLa cells and caused a cell arrest in S phase[4]. Treatment of C2C12 cells with 30µM Zidovudine for 8 days resulted in the accumulation of dysfunctional mitochondria and increased reactive oxygen species (ROS) production[5]. Treatment with 1000µM of Zidovudine for 5 weeks resulted in a decrease in checkpoint kinase 1 (Chk1) and checkpoint kinase 2 (Chk2) in NIH 3T3 cells and interference with cell cycle progression[6].
In vivo, Zidovudine treatment (50mg/kg twice daily; i.p.) for 4 weeks significantly resulted in a significant reduction in the levels of various inflammatory markers in the muscles of DMDmdx mouse model[7]. Male OF1 mice were treated with drinking water containing Zidovudine (10mg/kg; p.o.) for 35 days, causing oxidative damage to mitochondrial DNA in the liver of mice [8].
References:
[1] Sperling R. Zidovudine[J]. Infectious diseases in obstetrics and gynecology, 1998, 6(5): 197.
[2] Bianco M C A D, Inacio Leite D, Silva Castelo Branco F, et al. The use of Zidovudine pharmacophore in multi-target-directed ligands for AIDS therapy[J]. Molecules, 2022, 27(23): 8502.
[3] Gray L R, Tachedjian G, Ellett A M, et al. The NRTIs lamivudine, stavudine and zidovudine have reduced HIV-1 inhibitory activity in astrocytes[J]. PloS one, 2013, 8(4): e62196.
[4] Olivero O A, Tejera A M, Fernandez J J, et al. Zidovudine induces S-phase arrest and cell cycle gene expression changes in human cells[J]. Mutagenesis, 2005, 20(2): 139-146.
[5] Lin H, Stankov M V, Hegermann J, et al. Zidovudine-mediated autophagy inhibition enhances mitochondrial toxicity in muscle cells[J]. Antimicrobial Agents and Chemotherapy, 2019, 63(1): 10.1128/aac. 01443-18.
[6] Fang J L, McGarrity L J, Beland F A. Interference of cell cycle progression by zidovudine and lamivudine in NIH 3T3 cells[J]. Mutagenesis, 2009, 24(2): 133-141.
[7] Al-Khalidi R, Panicucci C, Cox P, et al. Zidovudine ameliorates pathology in the mouse model of Duchenne muscular dystrophy via P2RX7 purinoceptor antagonism[J]. Acta Neuropathologica Communications, 2018, 6(1): 27.
[8] de la Asunción J G, del Olmo M L, Sastre J, et al. Zidovudine (AZT) causes an oxidation of mitochondrial DNA in mouse liver[J]. Hepatology, 1999, 29(3): 985-987.
Zidovudine是一种合成核苷类似物，通过抑制逆转录酶阻断人类免疫缺陷病毒（HIV）的复制[1]。Zidovudine作为模型化合物被用于开发一系列相关衍生物以进行病毒抑制研究[2]。
在体外，Zidovudine处理48小时可显著抑制原代人胎儿星形胶质细胞（PFA）中的HIV-1活性，EC50值为1.311±0.130µM[3]。500μM的Zidovudine处理HeLa细胞24小时能诱导细胞周期蛋白D1上调并导致S期阻滞[4]。30µM的Zidovudine处理C2C12细胞8天会导致功能失调线粒体积累和活性氧（ROS）产生增加[5]。1000µM的Zidovudine处理NIH 3T3细胞5周可降低检查点激酶1（Chk1）和检查点激酶2（Chk2）水平，干扰细胞周期进程[6]。
在体内，DMDmdx小鼠模型每日两次腹腔注射Zidovudine（50mg/kg；持续4周）可显著降低肌肉中多种炎症标志物水平[7]。雄性OF1小鼠通过饮用水摄入Zidovudine（10mg/kg；持续35天）会引起肝脏线粒体DNA氧化损伤[8]。