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

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

Keywords: Drug repurposing; Fluvoxamine; · Breast cancer; · NUDT5; · Molecular dynamic simulation; MCF-7

Reference:

1. Ramasamy, Sumathi, Kanimozhi Jeyaram, Aathimoolam Narayanan, Sankarganesh Arunachalam, Selvarajan Ethiraj, Muthumanickam Sankar, and Boomi Pandian. "Repurposing fluvoxamine as an inhibitor for NUDT5 in breast cancer cell: an in silico and in vitro study." In Silico Pharmacology 13, no. 1 (2024): 5.