Study of anti-fibrillogenic activity of iron(II) clathrochelates.

Autor: Kovalska VB; Institute of Molecular Biology and Genetics NASU, 150 Zabolotnogo St., 03143 Kyiv, Ukraine. Electronic address: v.kovalska@gmail.com., Losytskyy MY; Institute of Molecular Biology and Genetics NASU, 150 Zabolotnogo St., 03143 Kyiv, Ukraine., Varzatskii OA; Institute of General and Inorganic Chemistry NASU, 32/34 Palladin Av., 03680 Kyiv, Ukraine., Cherepanov VV; Institute of Physics NASU, 46 Nauky Av., 03680 Kyiv, Ukraine., Voloshin YZ; Nesmeyanov Institute of Organoelement Compounds RAS, 28 Vavilova St., Moscow, Russia., Mokhir AA; Friedrich-Alexander-Universität Erlangen-Nürnberg, Department of Chemistry and Pharmacy, Organic Chemistry II, Henkestr. 42, Erlangen, Germany., Yarmoluk SM; Institute of Molecular Biology and Genetics NASU, 150 Zabolotnogo St., 03143 Kyiv, Ukraine., Volkov SV; Institute of General and Inorganic Chemistry NASU, 32/34 Palladin Av., 03680 Kyiv, Ukraine.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2014 Mar 15; Vol. 22 (6), pp. 1883-8. Date of Electronic Publication: 2014 Feb 02.
DOI: 10.1016/j.bmc.2014.01.048
Abstrakt: 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 ± 5 μM, respectively. The presence of clathrochelates decreases the fibril diameter from 5-12 nm for free insulin fibrils to 3-8 nm 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 © 2014 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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