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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.

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/df4f203e07f3/AN20758251-16-03-060-g001.jpg

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