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新型含硫代/缩氨基脲部分的白桦脂酸衍生物的设计与合成及其通过线粒体相关途径诱导细胞凋亡。

Design and Synthesis of Novel Betulin Derivatives Containing Thio-/Semicarbazone Moieties as Apoptotic Inducers through Mitochindria-Related Pathways.

机构信息

College of Pharmacy, Qiqihar Medical University, Qiqihar 161006, China.

Research Institute of Medicine & Pharmacy, Qiqihar Medical University, Qiqihar 161006, China.

出版信息

Molecules. 2021 Oct 21;26(21):6356. doi: 10.3390/molecules26216356.

DOI:10.3390/molecules26216356
PMID:34770765
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8587101/
Abstract

Two new series of betulin derivatives with semicarbazone (-) or thiosemicarbazone (-) groups at the C-28 position were synthesized. All compounds were evaluated for their in vitro cytotoxicities in human hepatocellular carcinoma cells (HepG2), human breast carcinoma cells (MCF-7), human lung carcinoma cells (A549), human colorectal cells (HCT-116) and normal human gastric epithelial cells (GES-1). Among these compounds, displayed the most potent cytotoxicity with an IC value of 5.86 ± 0.61 μM against MCF-7 cells. Furthermore, the preliminary mechanism studies in MCF-7 cells showed that compound could trigger the intracellular mitochondrial-mediated apoptosis pathway by losing MMP level, which was related with the upregulation of Bax, P53 and cytochrome c expression; the downregulation of Bcl-2 expression; activation of the expression levels of caspase-3, caspase-9, cleaved caspase-3 and cleaved caspase-9; and an increase in the amounts of intracellular reactive oxygen species. These results indicated that compound may be used as a valuable skeleton structure for developing novel antitumor agents.

摘要

合成了两个新型系列的桦木醇衍生物，其 C-28 位具有氨基甲脒（-）或硫代氨基甲脒（-）基团。所有化合物均在人肝癌细胞（HepG2）、人乳腺癌细胞（MCF-7）、人肺癌细胞（A549）、人结肠直肠癌细胞（HCT-116）和正常人胃上皮细胞（GES-1）中进行了体外细胞毒性评估。在这些化合物中，化合物 对 MCF-7 细胞表现出最强的细胞毒性，IC 值为 5.86±0.61μM。此外，在 MCF-7 细胞中的初步机制研究表明，化合物 可以通过降低 MMP 水平触发细胞内线粒体介导的凋亡途径，这与 Bax、P53 和细胞色素 c 表达上调、Bcl-2 表达下调、caspase-3、caspase-9、裂解 caspase-3 和裂解 caspase-9 的表达水平激活以及细胞内活性氧物质的增加有关。这些结果表明，化合物 可能可作为开发新型抗肿瘤药物的有价值的骨架结构。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/eff2bba3c63e/molecules-26-06356-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/364cf2991df6/molecules-26-06356-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/ee8310d6e425/molecules-26-06356-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/d965e6795ba1/molecules-26-06356-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/5c636c76adfb/molecules-26-06356-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/ca983657e647/molecules-26-06356-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/db28810d611e/molecules-26-06356-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/83868c1bfc4f/molecules-26-06356-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/8c5aa1039c64/molecules-26-06356-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/f4d559e20555/molecules-26-06356-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/351321b419dc/molecules-26-06356-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/eff2bba3c63e/molecules-26-06356-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/364cf2991df6/molecules-26-06356-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/ee8310d6e425/molecules-26-06356-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/d965e6795ba1/molecules-26-06356-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/5c636c76adfb/molecules-26-06356-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/ca983657e647/molecules-26-06356-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/db28810d611e/molecules-26-06356-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/83868c1bfc4f/molecules-26-06356-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/8c5aa1039c64/molecules-26-06356-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/f4d559e20555/molecules-26-06356-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/351321b419dc/molecules-26-06356-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f5/8587101/eff2bba3c63e/molecules-26-06356-g010.jpg

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本文引用的文献

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2
Glycoconjugation of Betulin Derivatives Using Copper-Catalyzed 1,3-Dipolar Azido-Alkyne Cycloaddition Reaction and a Preliminary Assay of Cytotoxicity of the Obtained Compounds.使用铜催化的1,3-偶极叠氮-炔环加成反应对桦木醇衍生物进行糖基化修饰及对所得化合物细胞毒性的初步测定。
Molecules. 2020 Dec 18;25(24):6019. doi: 10.3390/molecules25246019.
3
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Molecules. 2022 Oct 28;27(21):7326. doi: 10.3390/molecules27217326.
4
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Biomolecules. 2022 Oct 21;12(10):1540. doi: 10.3390/biom12101540.
5
Effect of Modified Levopimaric Acid Diene Adducts on Mitochondrial and Liposome Membranes.改性左旋海松酸二烯加合物对线粒体膜和脂质体膜的影响。
Membranes (Basel). 2022 Sep 8;12(9):866. doi: 10.3390/membranes12090866.
Plant extracts and betulin from Ligaria cuneifolia inhibit P-glycoprotein function in leukemia cells.
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4
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5
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6
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8
Effect of betulin and betulonic acid on isolated rat liver mitochondria and liposomes.桦木醇和桦木酸对离体大鼠肝线粒体和脂质体的影响。
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9
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10
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