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5'-去甲阿霉素的重新利用：知名的S-腺苷-L-高半胱氨酸水解酶抑制剂作为一种潜在的抗白血病药物。

5'-Noraristeromycin Repurposing: Well-known S-Adenosyl-L-homocysteine Hydrolase Inhibitor As a Potential Drug Against Leukemia.

作者信息

Novikova O N, Matyugina E S, Gorshenin A V, Velikorodnaya Yu I, Krengauz M D, Vedernikova V O, Spirin P V, Prassolov V S, Kochetkov S N, Khandazhinskaya A L

机构信息

Research Institute of Hygiene, Toxicology and Occupational Pathology, Federal Medical and Biological Agency, Volgograd, 400048 Russian Federation.

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russian Federation.

出版信息

Acta Naturae. 2024 Jul-Sep;16(3):60-66. doi: 10.32607/actanaturae.27443.

DOI:10.32607/actanaturae.27443
PMID:39555174
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11569843/
Abstract

5'-Noraristeromycin as a racemic mixture of enantiomers was found to exhibit a pronounced cytotoxic effect on leukemia cells; IC for the Jurkat, K562, and THP-1 cell lines was 7.3, 1.3, and 3.7 μM, respectively. The general toxicity of 5'-noraristeromycin was studied in experiments on white mice upon single-dose intragastric administration; toxicometric parameters were determined, and the clinical and pathomorphological presentation of acute intoxication was studied. LD of the substance was shown to be 63.2 (52.7÷75.8) mg/kg; LD16, 44.7 mg/kg, and LD84, 89.4 mg/kg. Administration of the substance at a dose within the studied dose range is accompanied by systemic damage to the internal organs and tissues of the experimental animals.

摘要

5'-去甲阿霉素作为对映体的外消旋混合物，对白血病细胞表现出显著的细胞毒性作用；对Jurkat、K562和THP-1细胞系的半数抑制浓度（IC）分别为7.3、1.3和3.7 μM。在对白鼠进行单剂量灌胃给药的实验中研究了5'-去甲阿霉素的一般毒性；测定了毒理学参数，并研究了急性中毒的临床和病理形态学表现。该物质的半数致死量（LD）显示为63.2（52.7÷75.8）mg/kg；16%致死剂量（LD16）为44.7 mg/kg，84%致死剂量（LD84）为89.4 mg/kg。在研究的剂量范围内给药该物质会对实验动物的内脏器官和组织造成全身性损害。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8092/11569843/125f27c9b23c/AN20758251-16-03-060-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8092/11569843/df4f203e07f3/AN20758251-16-03-060-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8092/11569843/d75f7873ac34/AN20758251-16-03-060-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8092/11569843/997af965d140/AN20758251-16-03-060-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8092/11569843/0cb37d0a9c60/AN20758251-16-03-060-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8092/11569843/125f27c9b23c/AN20758251-16-03-060-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8092/11569843/df4f203e07f3/AN20758251-16-03-060-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8092/11569843/d75f7873ac34/AN20758251-16-03-060-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8092/11569843/997af965d140/AN20758251-16-03-060-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8092/11569843/0cb37d0a9c60/AN20758251-16-03-060-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8092/11569843/125f27c9b23c/AN20758251-16-03-060-g005.jpg

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The Antitumoral Effect of the S-Adenosylhomocysteine Hydrolase Inhibitor, 3-Deazaneplanocin A, is Independent of EZH2 but is Correlated with EGFR Downregulation in Chondrosarcomas.S-腺苷同型半胱氨酸水解酶抑制剂3-去氮杂氮胞苷A在软骨肉瘤中的抗肿瘤作用不依赖于EZH2，但与表皮生长因子受体下调相关。
Cell Physiol Biochem. 2019;53(4):731-745. doi: 10.33594/000000168.
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Aristeromycin and DZNeP cause growth inhibition of prostate cancer via induction of mir-26a.
阿瑞斯特霉素和 DZNeP 通过诱导 mir-26a 抑制前列腺癌的生长。
Eur J Pharmacol. 2017 Oct 5;812:138-146. doi: 10.1016/j.ejphar.2017.07.023. Epub 2017 Jul 10.
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Effectiveness of imatinib mesylate over etoposide in the treatment of sensitive and resistant chronic myeloid leukaemia cells .甲磺酸伊马替尼对比依托泊苷治疗敏感及耐药慢性髓性白血病细胞的疗效
Exp Ther Med. 2017 Jun;13(6):3209-3216. doi: 10.3892/etm.2017.4443. Epub 2017 May 8.
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Identification of AHCY inhibitors using novel high-throughput mass spectrometry.使用新型高通量质谱法鉴定腺苷高半胱氨酸水解酶抑制剂
Biochem Biophys Res Commun. 2017 Sep 9;491(1):1-7. doi: 10.1016/j.bbrc.2017.05.107. Epub 2017 May 19.
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Metabolic perturbation of epigenome by inhibiting S-adenosylhomocysteine hydrolase elicits senescence through DNA damage response in hepatoma cells.通过抑制S-腺苷同型半胱氨酸水解酶对表观基因组进行代谢扰动，可通过肝癌细胞中的DNA损伤反应引发细胞衰老。
Tumour Biol. 2017 May;39(5):1010428317699117. doi: 10.1177/1010428317699117.
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