RT Journal Article
T1 Discovery of a potent melatonin-based inhibitor of quinone reductase-2 with neuroprotective and neurogenic properties
A1 Herrera Arozamena, C.
A1 Estrada Valencia, M
A1 García Díez, G.
A1 Pérez, C.
A1 León, R.
A1 Infantes, L.
A1 Morales García, José Ángel
A1 Pérez Castillo, Ana
A1 Sastre, E. del
A1 López, M.G.
A1 Rodríguez Franco, M.I.
AB 5-Methoxy-3-(5-methoxyindolin-2-yl)-1H-indole (3), whose structure was unambiguously elucidated by X-ray analysis, was identified as a multi-target compound with potential application in neurodegenerative diseases. It is a low nanomolar inhibitor of QR2 (IC50 = 7.7 nM), with greater potency than melatonin and comparable efficacy to the most potent QR2 inhibitors described to date. Molecular docking studies revealed the potential binding mode of 3 to QR2, which explains its superior potency compared to melatonin. Furthermore, compound 3 inhibits hMAO-A, hMAO-B and hLOX-5 in the low micromolar range and is an excellent ROS scavenger. In phenotypic assays, compound 3 showed neuroprotective activity in a cellular model of oxidative stress damage, it was non-toxic, and was able to activate neurogenesis from neural stem-cell niches of adult mice. These excellent biological properties, together with its both good in silico and in vitro drug-like profile, highlight compound 3 as a promising drug candidate for neurodegenerative diseases.
YR 2024
FD 2024
LK https://hdl.handle.net/20.500.14352/110934
UL https://hdl.handle.net/20.500.14352/110934
LA eng
NO Herrera-Arozamena C, Estrada-Valencia M, García-Díez G, Pérez C, León R, Infantes L, Morales-García JA, Pérez-Castillo A, Del Sastre E, López MG, Rodríguez-Franco MI. Discovery of a potent melatonin-based inhibitor of quinone reductase-2 with neuroprotective and neurogenic properties. Eur J Med Chem. 2024 Nov 5;277:116763. doi: 10.1016/j.ejmech.2024.116763. Epub 2024 Aug 10. PMID: 39146834.
DS Docta Complutense
RD 10 abr 2025