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The series of the β-ketoenoles (2 E ,5 Z ,7 E ,9 E )-2-(alkylamino)-6-hydroxy-10-phenyldeca-2,5,7,9-tetraen-4-ones with variation of the alkylamino tail groups was synthesized and studied as potential probes for the sensing of protein insoluble aggregates - amyloid fibrils. Depending on the structure of the alkylamino group, the dyes could increase their fluorescence intensity in the dozens of times in the presence of insulin fibrils. The compound with a 2-hydroxyethylamino substituent demonstrates the highest fluorescence response (up to 60 times) and good range of insulin fibril detection (1–50 μg/ml). In complexes with fibrils, the dyes possess fluorescence quantum yield values up to 15% and binding constant values of about 2 × 10 5 M −1 . The excitation and emission maxima of β-ketoenoles are located in the range 407–427 nm and 500–554 nm correspondingly. These compounds are weakly fluorescent when free and slightly sensitive to the native proteins insulin and bovine serum albumin. Thus β-ketoenoles are considered as prospective molecules for the fluorescent detection of amyloid aggregates of proteins. [ABSTRACT FROM AUTHOR]

Abstract: The macrocyclic compounds mono- and bis-iron(II) clathrochelates were firstly studied as potential anti-fibrillogenic agents using fluorescent inhibitory assay, atomic force microscopy and flow cytometry. It is shown that presence of the clathrochelates leads to the change in kinetics of insulin fibrillization reaction and reduces the amount of formed fibrils (up to 70%). The nature of ribbed substituent could determine the activity of clathrochelates—the higher inhibitory effect is observed for compounds containing carboxybenzenesulfide groups, while the inhibitory properties only slightly depend on the size of complex species. The mono- and bis-clathrochelate derivatives of meta-mercaptobenzoic acid have close values of IC50 namely 16±2 and 24±5μM, respectively. The presence of clathrochelates decreases the fibril diameter from 5-12nm for free insulin fibrils to 3–8nm for these formed in the clathrochelate presence, it also prevents the lateral aggregation of mature fibrils and formation of superfibrillar clusters. However the addition of clathrochelate results in more heterogeneous (both by size and structure) insulin aggregates population as compared to the free insulin. This way, cage complexes—iron(II) clathrochelates are proposed as efficient agents able to suppress the protein aggregation processes. [Copyright &y& Elsevier]