Curcumin derivatives and Aβ-fibrillar aggregates: An interactions' study for diagnostic/therapeutic purposes in neurodegenerative diseases

Bioorganic & Medicinal Chemistry
Giulia OrtecaMaria Cristina Menziani

Abstract

Several neurodegenerative diseases, like Alzheimer's (AD), are characterized by amyloid fibrillar deposition of misfolded proteins, and this feature can be exploited for both diagnosis and therapy design. In this paper, structural modifications of curcumin scaffold were examined in order to improve its bioavailability and stability in physiological conditions, as well as its ability to interfere with β-amyloid fibrils and aggregates. The acid-base behaviour of curcumin derivatives, their pharmacokinetic stability in physiological conditions, and in vitro ability to interfere with Aβ fibrils at different incubation time were investigated. The mechanisms governing these phenomena have been studied at atomic level by means of molecular docking and dynamic simulations. Finally, biological activity of selected curcuminoids has been investigated in vitro to evaluate their safety and efficiency in oxidative stress protection on hippocampal HT-22 mouse cells. Two aromatic rings, π-conjugated structure and H-donor/acceptor substituents on the aromatic rings showed to be the sine qua non structural features to provide interaction and disaggregation activity even at very low incubation time (2h). Computational simulations proved that upon...Continue Reading

Citations

Oct 1, 2019·Physical Chemistry Chemical Physics : PCCP·Shivani Gupta, Ashok Kumar Dasmahapatra
Mar 19, 2020·International Journal of Molecular Sciences·Eirini Chainoglou, Dimitra Hadjipavlou-Litina
Aug 25, 2020·Physical Chemistry Chemical Physics : PCCP·Shivani Gupta, Ashok Kumar Dasmahapatra
Sep 13, 2018·International Journal of Molecular Sciences·Sofia GiorgettiFrancesco Antonio Aprile
Dec 24, 2018·International Journal of Molecular Sciences·Silvia BellutiCarol Imbriano
Aug 6, 2020·International Journal of Molecular Sciences·Francesco TavantiMaria Cristina Menziani
Dec 19, 2020·Comprehensive Reviews in Food Science and Food Safety·Ana Sanches SilvaSeyed Mohammad Nabavi
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Sep 15, 2020·ACS Chemical Neuroscience·Francesco TavantiAlfredo Alexander-Katz
Dec 4, 2021·Journal of Biomolecular Structure & Dynamics·Shivani Gupta, Ashok Kumar Dasmahapatra

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