Abstract

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 alpha-synuclein and the hydrophobic peptide (71)VTGVTAVAQKTV(82) including flavonols (kaempferol, quercetin, and isorhamnetin), isoflavone (genistein) and flavone (luteolin), and compounds with alpha, beta unsaturated carbonyl moieties such as chlorogenic acid and the depsidone fumarprotocetraric acid. Most compounds inhibit both alpha-synuclein and hydrophobic peptide fibrillization. Moreover, ITC experiments showed a Kd varying from 9 to 20 mu M, and Delta H 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 alpha-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 alpha-synuclein and stimulate the catecholamines pathway is promising.