TY - JOUR
T1 - The Key Features of Catechols and α,β Unsaturated Carbonyl Moieties
T2 - Interaction With α-syn Hydrophobic peptide and Activation of Catecholamines Pathway in Cells
AU - Monroy-Moya, S.
AU - Caballero, J.
AU - González-Norambuena, F.
AU - Simirgiotis, M.
AU - Sánchez, E.
AU - Areche, C.
AU - Fuentealba, D.
AU - Cornejo, A.
N1 - Publisher Copyright:
© 2023 Wiley-VCH GmbH.
PY - 2023/5/19
Y1 - 2023/5/19
N2 - Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide, and the treatment focuses on delivering L-DOPA. In this work, we isolated and tested several compounds against α-synuclein and the hydrophobic peptide 71VTGVTAVAQKTV82 including flavonols (kaempferol, quercetin, and isorhamnetin), isoflavone (genistein) and flavone (luteolin), and compounds with α, β unsaturated carbonyl moieties such as chlorogenic acid and the depsidone fumarprotocetraric acid. Most compounds inhibit both α-synuclein and hydrophobic peptide fibrillization. Moreover, ITC experiments showed a Kd varying from 9 to 20 μM, and ΔH values vary from −1.94 to −10.5 among the compounds. Docking experiments showed the intermolecular interactions within the sites 2, 9, and 3/13 of α-synuclein, and with the hydrophobic peptide. In cultured cells, the presence of the compounds showed that most of them can promote cell proliferation and differentiation. Considering that treatments for neurodegenerative disorders, including PD, is only palliative the evaluation of these compounds that can prevent the fibrillization of α-synuclein and stimulate the catecholamines pathway is promising.
AB - Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide, and the treatment focuses on delivering L-DOPA. In this work, we isolated and tested several compounds against α-synuclein and the hydrophobic peptide 71VTGVTAVAQKTV82 including flavonols (kaempferol, quercetin, and isorhamnetin), isoflavone (genistein) and flavone (luteolin), and compounds with α, β unsaturated carbonyl moieties such as chlorogenic acid and the depsidone fumarprotocetraric acid. Most compounds inhibit both α-synuclein and hydrophobic peptide fibrillization. Moreover, ITC experiments showed a Kd varying from 9 to 20 μM, and ΔH values vary from −1.94 to −10.5 among the compounds. Docking experiments showed the intermolecular interactions within the sites 2, 9, and 3/13 of α-synuclein, and with the hydrophobic peptide. In cultured cells, the presence of the compounds showed that most of them can promote cell proliferation and differentiation. Considering that treatments for neurodegenerative disorders, including PD, is only palliative the evaluation of these compounds that can prevent the fibrillization of α-synuclein and stimulate the catecholamines pathway is promising.
KW - Cell differentiation
KW - Hydrophobic region
KW - Non-covalent interactions
KW - Parkinson's disease
KW - Tyrosine hydroxylase
UR - http://www.scopus.com/inward/record.url?scp=85159865826&partnerID=8YFLogxK
U2 - 10.1002/slct.202301106
DO - 10.1002/slct.202301106
M3 - Article
AN - SCOPUS:85159865826
SN - 2365-6549
VL - 8
JO - ChemistrySelect
JF - ChemistrySelect
IS - 19
M1 - e202301106
ER -