2. Academic Validation
  3. (E)-3-Heteroarylidenechroman-4-ones as potent and selective monoamine oxidase-B inhibitors

(E)-3-Heteroarylidenechroman-4-ones as potent and selective monoamine oxidase-B inhibitors

  • Eur J Med Chem. 2016 Jul 19:117:292-300. doi: 10.1016/j.ejmech.2016.03.081.
Nicoletta Desideri 1,  Luca Proietti Monaco 2,  Rossella Fioravanti 2,  Mariangela Biava 2,  Matilde Yáñez 3,  Stefano Alcaro 4,  Francesco Ortuso 4
Affiliations

Affiliations

  • 1 Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza - Università di Roma, P.le Aldo Moro, 5, 00185, Rome, Italy. Electronic address: nicoletta.desideri@uniroma1.it.
  • 2 Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza - Università di Roma, P.le Aldo Moro, 5, 00185, Rome, Italy.
  • 3 Departamento de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, Campus Universitario Sur, E-15782, Santiago de Compostela (La Coruña), Spain.
  • 4 Dipartimento di Scienze della Salute, Università"Magna Græcia" di Catanzaro, Campus Universitario "S. Venuta", Viale Europa, 88100, Catanzaro, Italy.
PMID: 27135371 DOI: 10.1016/j.ejmech.2016.03.081
Abstract

A series of (E)-3-heteroarylidenechroman-4-ones (1a-r) was designed, synthesized and investigated in vitro for their ability to inhibit the enzymatic activity of both human Monoamine Oxidase (hMAO) isoforms, hMAO-A and hMAO-B. All the compounds were found to be selective hMAO-B inhibitors showing IC50 values in the nanomolar or micromolar range. (E)-5,7-Dichloro-3-{[(2-(dimethylamino)pyrimidin-5-yl]methylene}chroman-4-one (1c) was the most interesting compound identified in this study, endowed with higher hMAO-B potency (IC50 = 10.58 nM) and selectivity (SI > 9452) with respect to the reference selective inhibitor selegiline (IC50 = 19.60 nM, IC50 > 3431). Molecular modelling studies were performed for rationalizing at molecular level the target selective inhibition of our compounds, revealing a remarkable contribution of hydrogen bond network and water solvent.

Keywords

Chroman-4-ones; Docking studies; Homoisoflavonoids; Monoamine oxidases; Selective hMAO-B inhibitors.

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