Ramasamy Sumathi, Jeyaram Kanimozhi, Narayanan Aathimoolam, Arunachalam Sankarganesh, Ethiraj Selvarajan, Sankar Muthumanickam, Pandian Boomi
Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil, 626126 Tamil Nadu India.
Department of Life Sciences, Christ University, Bengaluru, 560029 Karnataka India.
In Silico Pharmacol. 2024 Dec 24;13(1):5. doi: 10.1007/s40203-024-00293-2. eCollection 2025.
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.
Effect of fluvoxamine on breast cancer cells.
药物重新利用对于加速药物研发和满足药物需求是必要的。本研究调查了使用氟伏沙明抑制乳腺癌细胞中细胞代谢酶NUDT5的可能性。采用计算和实验技术来评估药物的结构灵活性、结合稳定性和化学反应性。这些发现表明，氟伏沙明有效地抑制了NUDT5的活性，结合分数为 - 8.514千卡/摩尔证明了这一点。此外，氟伏沙明与NUDT5的结合位置得到了优化。已表明氟伏沙明附着于NUDT5中Trp28、Trp46、Glu47、Arg51、Arg84和Leu98的活性位点会改变ADPr的代谢。这些改变在乳腺癌细胞的ATP产生中起作用。此外，使用氟伏沙明对MCF - 7细胞系进行的MTT试验显示IC50值为53.86±0.05微摩尔。AO/EtBr和DAPI染色证实了氟伏沙明诱导的细胞凋亡。
氟伏沙明对乳腺癌细胞的影响。
