9R3K
Crystal structure of human MAO B in complex with ((E)-3-(3-nitrophenyl)-1-(3-(trifluoromethyl)phenyl)prop-2-en-1-one (4b)
This is a non-PDB format compatible entry.
Summary for 9R3K
| Entry DOI | 10.2210/pdb9r3k/pdb |
| Descriptor | Amine oxidase [flavin-containing] B, FLAVIN-ADENINE DINUCLEOTIDE, (~{E})-3-[3-[oxidanyl(oxidanylidene)-$l^{4}-azanyl]phenyl]-1-[3-(trifluoromethyl)phenyl]prop-2-en-1-one, ... (5 entities in total) |
| Functional Keywords | monoamine oxidase, chalcone, neuroprotective drug, flavoprotein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 120299.77 |
| Authors | |
| Primary citation | Facchetti, G.,Marchese, S.,Cocce, V.,Doneda, L.,Alessandri, G.,Paino, F.,Pessina, A.,Pinzi, L.,Rastelli, G.,Binda, C.,Christodoulou, M.S.,Rimoldi, I. Design, synthesis, and biological evaluation of chalcone derivatives as selective Monoamine Oxidase-B inhibitors with potential neuroprotective effects. Eur.J.Med.Chem., 298:117990-117990, 2025 Cited by PubMed Abstract: A series of chalcone derivatives was synthesized via Claisen-Schmidt condensation and further modified through selective reductions and amide couplings to explore their potential as monoamine oxidase B (MAO-B) inhibitors. Screening against recombinant human MAO-B identified compounds 4a, 4b, 4e, and 5a as potent inhibitors, showing submicromolar inhibition constants (K). Structure-activity relationship (SAR) analysis emphasized the relevance of a planar α,β-unsaturated carbonyl and specific aromatic substitutions for activity. Crystallographic studies showed conserved binding modes in the MAO-B active site, while computational analyses confirmed favourable interactions and conformational flexibility of compound 5a. Cytotoxicity assays in normal and cancer cell lines indicated minimal toxicity for 5a. Notably, 5a also exhibited neuroprotective effects in SH-SY5Y cells exposed to 6-hydroxydopamine (6-OHDA), a model of Parkinson's disease. These findings demonstrated the importance of structural fine-tuning within the chalcone scaffold to achieve MAO-B selectivity and identify compound 5a as a promising, non-toxic candidate for neurodegenerative disease treatment. PubMed: 40738081DOI: 10.1016/j.ejmech.2025.117990 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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