28WL

Crystal structure of human Monoamine Oxidase B (MAO B) in complex with 7-[(4-{[(3,4-dimethoxybenzyl(methyl)amino]methyl}benzyl)oxy]-4-(hydroxymethyl)-2H-chromen-2-one) (LP1488)

This is a non-PDB format compatible entry.

Summary for 28WL

• Entry DOI: 10.2210/pdb28wl/pdb
• Descriptor: Amine oxidase [flavin-containing] B, FLAVIN-ADENINE DINUCLEOTIDE, 7-[[4-[[(3,4-dimethoxyphenyl)methyl-methyl-amino]methyl]phenyl]methoxy]-4-(hydroxymethyl)chromen-2-one, ... (6 entities in total)
• Functional Keywords: monoamine oxidase, inhibitor, drug design, alzheimer, multitarget, flavoprotein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 121147.02

Authors

Marchese, S.,Gottinger, A.,Pisani, L.,Binda, C. (deposition date: 2026-02-24, release date: 2026-05-27, Last modification date: 2026-06-17)

Primary citation

Rullo, M.,La Spada, G.,Brazzolotto, X.,Marchese, S.,El Idrissi, I.G.,Miciaccia, M.,Colella, M.,Brea, J.M.,Macchia, E.,Loza, M.I.,Gottinger, A.,Scilimati, A.,Perrone, M.G.,Stefanachi, A.,Binda, C.,Leonetti, F.,Pisani, L.
Leveraging multitargeting BChE-MAO B inhibitors against microglia-related neuroinflammation: in vitro biological evaluation, structure-activity relationships, drug-like properties, and X-ray crystal complexes.
Eur.J.Med.Chem., 316:118961-118961, 2026

PubMed Abstract: Neuroinflammatory process is a key factor in multifaceted neurodegenerative disorders, as proved by the increased levels of pro-inflammatory mediators, primarily released by microglia and astrocytes. Following a multitarget strategy, we aimed at identifying dual inhibitors of butyrylcholinesterase (BChE) and monoamine oxidase B (MAO B). Both enzymes emerged as promising targets for tuning the inflammatory response within the central nervous system (CNS). Here we describe the synthesis, in vitro biological evaluation, and drug-likeness characterization of a series of 16 methoxy-bearing coumarin derivatives. Among them, compound 9 behaved as a well-balanced dual-acting inhibitor (hBChE, IC = 557 nM; hMAO B, IC = 142 nM) capable of mitigating interleukin-6 release from stimulated human microglia clone 3 (HMC3) cells in a dose-dependent manner and of counteracting 6-hydroxydopamine (6-OHDA) toxicity in SH-SY5Y neuroblastoma cell lines. Moreover, X-ray crystal structures of 9 in both hBChE and hMAO B were solved at 2.36 Å and 1.60 Å resolution, respectively.

PubMed: 42241774
DOI: 10.1016/j.ejmech.2026.118961

Experimental method

X-RAY DIFFRACTION (1.6 Å)