Products Cited in Publications Worldwide Ruthenium(iii) complexes containing thiazole-based ligands that modulate amyloid-β aggregation

Ruthenium(iii) complexes containing thiazole-based ligands that modulate amyloid-β aggregation

Huffman, Samantha E.; Yawson, Gideon K.; Fisher, Samuel S.; Bothwell, Paige J.; Platt, David C.; Jones, Marjorie A.; Hamaker, Christopher G.; Webb, Michael I.

DOI: PMID:

Abstract

Metal-based therapeutics are uniquely suited to target soluble Aβ and have shown considerable promise to prevent the aggregation and induced cytotoxicity of the peptide in vitro. Herein, we have prepared a small series of derivatives of two promising Ru(III) complexes NAMI-A (imidazolium [trans-RuCl4(1H-imidazole)(DMSO-S)]) and PMRU20 (2-aminothiazolium [trans-RuCl4(2-aminothiazole)2]), to determine structure-activity relationships (SAR) for Ru(III) therapeutics for Alzheimer's Disease. Using the three complementary methods of Thioflavin T fluorescence, dynamic light scattering (DLS), and transmission electron microscopy (TEM), it was determined that the symmetry around the metal center did not significantly impact the activity of the complexes, but rather the attached thiazole ligand(s) mitigated Aβ aggregation. Across both families of Ru(III) complexes the determined SAR for the functional groups on the thiazole ligands to modulate Aβ aggregation were NH2 > CH3 > H. These results highlight the importance of secondary interactions between the metallotherapeutic and the Aβ peptide where hydrogen-bonding has the greatest impact on modulating Aβ aggregation.

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Aminothiazole

A12899696-50-498%

Aminothiazole

10.0/25g

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