Anti-amyloidogenic and fibril-destabilizing effects of two manganese-salen derivatives against hen egg-white lysozyme aggregation

Amyloid depositions of proteins play crucial roles in a wide variety of degenerative disorders called amyloidosis. In the present study, we used hen egg white lysozyme (HEWL), as an in vitro model system, to induce fibrillation under high temperatures and acidic pH conditions, and investigated the inhibitory and disruptive effects of two salen-manganese complexes, namely EUK-8 and EUK-134, with aromatic structures, against fibrilization. Results of this study showed that EUK-8 and EUK-134 in a dose-dependent manner inhibited the HEWL aggregation. Similar results were obtained when these compounds were added to pre-formed amyloid fibrils. Docking results also demonstrated that the aromatic rings of EUK-8 and EUK-134 interact with the hydrophobic region of lysozyme via Van der Waals interactions. Results of MTT assay indicated that addition of pre-formed fibrils treated with EUK-8 and EUK-134 at doses 1:1 and 5:1 mM; drug to protein, to SK-N-MC cells significantly increased the viability of cells, compared to the fibril sample alone. Based on these results, it might be concluded that in addition to inherent hydrophobicity associated with the ligand section of each of the derivatives, electron density around the central metal ion of the derivatives contributes to lower lysozyme fibril accumulation.