Inhibition of Amyloid-β Aggregation by Cobalt(III) Schiff Base Complexes: A Computational and Experimental Approach
Journal of the American Chemical Society, cilt.141, sa.42, ss.16685-16695, 2019 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 141 Sayı: 42
- Basım Tarihi: 2019
- Doi Numarası: 10.1021/jacs.9b06388
- Dergi Adı: Journal of the American Chemical Society
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.16685-16695
- Boğaziçi Üniversitesi Adresli: Evet
Özet
Coordination complexes have emerged as prominent modulators of amyloid aggregation via their interaction with the N-terminal histidine residues of amyloid-β (Aβ). Herein, we report the synthesis and characterization of a novel cobalt(III) Schiff base complex with methylamine axial ligands, and we present both computational and experimental data demonstrating the reduction of β-sheet formation by this complex. The computations include molecular dynamics simulations of both monomeric and pentameric Aβ, which demonstrate decreased formation of β-sheet structures, destabilization of preformed β-sheets, and suppression of aggregation. These results are consistent with a dose dependence in experimental bulk aggregation data using thioflavin T fluorescence, and overall this study demonstrates useful drug activity of the cobalt complex.