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镍(II)脯氨酸二硫代氨基甲酸盐对 MCF-7 乳腺癌细胞细胞毒性的整合分子对接和实验分析。

Integrated Molecular Docking and Experimental Analysis of Ni(II) Proline Dithiocarbamate Cytotoxicity in MCF-7 Breast Cancer Cells.

机构信息

Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.

Bosowa School Makassar, Makassar, Indonesia.

出版信息

Asian Pac J Cancer Prev. 2024 Oct 1;25(10):3481-3487. doi: 10.31557/APJCP.2024.25.10.3481.


DOI:10.31557/APJCP.2024.25.10.3481
PMID:39471014
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11711347/
Abstract

OBJECTIVE: Chemotherapy is one of the most effective and widely used treatment types for breast cancer. The Ni(II) proline dithiocarbamate (Ni(II)ProDtc) complex has been synthesized as a potential anticancer agent with minimal systemic toxicity. The dithiocarbamate ligand, combined with the amino acid proline, holds promise as a radio chemotherapeutic target agent in tumors. The anticancer activity of a Ni(II) complex compound with a proline dithiocarbamate ligand was tested on the MCF-7 breast cancer cell line as part of a study on essential metal-based therapeutics. METHODS: Molecular docking studies identified the active sites for the estradiol-estrogen receptor-α protein. The Ni(II)ProDtc complex was synthesized and characterized using melting point analysis, conductivity measurements, UV-Vis spectroscopy, and FT-IR spectroscopy. The cytotoxicity of the complex was evaluated in vitro using the MCF-7 breast cancer cell line. RESULTS: The UV-Vis spectrum at 246 nm indicated the π→π* intraligand transition of the CS2 group, while FT-IR analysis revealed peaks at 364-457 cm-1 corresponding to the bonding between Ni and Sulfur (S) and Oxygen (O) from proline. Further, the UV-Vis spectrum displayed bands at 212 and 676 nm, and FT-IR data at 387-691 cm-1, confirming the coordination of the Ni(II) atoms with sulfur, nitrogen, and oxygen in the isoleucine dithiocarbamate ligand. In vitro, cytotoxicity tests revealed that Ni(II)ProDtc induced cell death in the breast cancer cell line, showing significant morphological changes in MCF-7 cancer cells, with an IC50 value of 315.70 µg/mL. CONCLUSION: The Ni(II)ProDtc complex was successfully synthesized and demonstrates anticancer activity in MCF-7 breast cancer cells, indicating significant potential as an anticancer agent for breast cancer.

摘要

目的:化疗是乳腺癌最有效和最广泛使用的治疗类型之一。镍(II)脯氨酸二硫代氨基甲酸盐(Ni(II)ProDtc)复合物已被合成作为一种潜在的抗癌药物,具有最小的全身毒性。二硫代氨基甲酸盐配体与氨基酸脯氨酸结合,有望成为肿瘤中放射化疗的靶标。作为基于必需金属的治疗研究的一部分,对具有脯氨酸二硫代氨基甲酸盐配体的 Ni(II)配合物的抗癌活性在 MCF-7 乳腺癌细胞系上进行了测试。

方法:分子对接研究确定了雌二醇-雌激素受体-α蛋白的活性部位。使用熔点分析、电导率测量、紫外可见光谱和傅里叶变换红外光谱对 Ni(II)ProDtc 配合物进行了合成和表征。使用 MCF-7 乳腺癌细胞系评估了该配合物的体外细胞毒性。

结果:在 246nm 处的紫外可见光谱表明 CS2 基团的π→π* 内配位体跃迁,而傅里叶变换红外分析显示在 364-457cm-1 处有峰,对应于 Ni 与硫(S)和氧(O)从脯氨酸键合。此外,紫外可见光谱在 212 和 676nm 处显示谱带,傅里叶变换红外数据在 387-691cm-1 处显示谱带,证实了 Ni(II)原子与异亮氨酸二硫代氨基甲酸盐配体中的硫、氮和氧的配位。在体外,细胞毒性试验表明,Ni(II)ProDtc 诱导乳腺癌细胞系中的细胞死亡,在 MCF-7 癌细胞中显示出显著的形态变化,IC50 值为 315.70µg/mL。

结论:成功合成了 Ni(II)ProDtc 配合物,并在 MCF-7 乳腺癌细胞中显示出抗癌活性,表明其作为乳腺癌抗癌药物具有显著的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef62/11711347/11acbeec729a/APJCP-25-3481-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef62/11711347/f54559eaeaa1/APJCP-25-3481-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef62/11711347/9c2899ae0d5c/APJCP-25-3481-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef62/11711347/0f1e85d6c737/APJCP-25-3481-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef62/11711347/b04776b02a89/APJCP-25-3481-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef62/11711347/dad614ab7e70/APJCP-25-3481-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef62/11711347/11acbeec729a/APJCP-25-3481-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef62/11711347/f54559eaeaa1/APJCP-25-3481-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef62/11711347/9c2899ae0d5c/APJCP-25-3481-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef62/11711347/0f1e85d6c737/APJCP-25-3481-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef62/11711347/b04776b02a89/APJCP-25-3481-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef62/11711347/dad614ab7e70/APJCP-25-3481-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef62/11711347/11acbeec729a/APJCP-25-3481-g006.jpg

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本文引用的文献

[1]
Investigations of Ni(II)Cysteine-Tyrosine Dithiocarbamate Complex: Synthesis, Characterization, Molecular Docking, Molecular Dynamic, and Anticancer Activity on MCF-7 Breast Cancer Cell Line.

Asian Pac J Cancer Prev. 2024-4-1

[2]
Synthesis, characterization, molecular docking studies of Mn(II)Prolinedithiocarbamate and its potential as anticancer agents.

Mol Divers. 2024-4

[3]
Multi- class classification of breast cancer abnormalities using Deep Convolutional Neural Network (CNN).

PLoS One. 2021

[4]
The comparison of Zn(II) arginine dithiocarbamate cytotoxicity in T47D breast cancer and fibroblast cells.

Breast Dis. 2021

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Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.

CA Cancer J Clin. 2021-5

[6]
Potential anticancer activity of Mn (II) complexes containing arginine dithiocarbamate ligand on MCF-7 breast cancer cell lines.

Ann Med Surg (Lond). 2020-11-11

[7]
α-Mangostin and its derivatives against estrogen receptor alpha.

J Biomol Struct Dyn. 2022-4

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O-Methylguanine-DNA Methyltransferase (MGMT): Challenges and New Opportunities in Glioma Chemotherapy.

Front Oncol. 2020-1-17

[9]
Au(iii)-Proline derivatives exhibiting selective antiproliferative activity against HepG2/SB3 apoptosis-resistant cancer cells.

Dalton Trans. 2019-10-10

[10]
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