Repurposing fluvoxamine as an inhibitor for NUDT5 in breast cancer cell: an in silico and in vitro study.

In silico pharmacology Pub Date : 2024-12-24 eCollection Date: 2025-01-01 DOI:10.1007/s40203-024-00293-2

Sumathi Ramasamy, Kanimozhi Jeyaram, Aathimoolam Narayanan, Sankarganesh Arunachalam, Selvarajan Ethiraj, Muthumanickam Sankar, Boomi Pandian

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Abstract

Drug repurposing is necessary to accelerate drug discovery and meet the drug needs. This study investigated the possibility of using fluvoxamine to inhibit the cellular metabolizing enzyme NUDT5 in breast cancer. Computational and experimental techniques were used to evaluate the structural flexibility, binding stability, and chemical reactivity of the drugs. These findings indicated that fluvoxamine effectively suppressed the activity of NUDT5, as evidenced by a binding score of - 8.514 kcal/mol. Furthermore, the binding positions of fluvoxamine and NUDT5 were optimized. Fluvoxamine attachment to the active sites of Trp28, Trp46, Glu47, Arg51, Arg84, and Leu98 in NUDT5 has been shown to alter the metabolism of ADPr. These alterations play a role in ATP production in the breast cancer cells. In addition, an MTT assay conducted on the MCF-7 cell line using fluvoxamine revealed an IC50 value of 53.86 ± 0.05 µM. Fluvoxamine-induced apoptosis was confirmed as evidenced by AO/EtBr and DAPI staining.

Graphical abstract: Effect of fluvoxamine on breast cancer cells.

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重新利用氟伏沙明作为乳腺癌细胞中NUDT5的抑制剂：一项计算机和体外研究。

药物再利用是加速药物发现和满足药物需求的必要条件。本研究探讨了氟伏沙明抑制乳腺癌细胞代谢酶NUDT5的可能性。采用计算和实验技术评价了药物的结构柔韧性、结合稳定性和化学反应性。这些结果表明，氟伏沙明有效抑制NUDT5的活性，其结合分数为- 8.514 kcal/mol。进一步优化了氟伏沙明与NUDT5的结合位置。氟伏沙明附着在NUDT5中Trp28、Trp46、Glu47、Arg51、Arg84和Leu98的活性位点上，已被证明可以改变ADPr的代谢。这些改变在乳腺癌细胞中ATP的产生中起作用。此外，使用氟伏沙明对MCF-7细胞系进行MTT检测，IC50值为53.86±0.05µM。AO/EtBr和DAPI染色证实氟伏沙明诱导的细胞凋亡。图形摘要：氟伏沙明对乳腺癌细胞的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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In silico pharmacology

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