title: Study of anti-fibrillogenic activity of iron(II) clathrochelates.
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 ± 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.
authors.affiliation: Institute of Molecular Biology and Genetics NASU, 150 Zabolotnogo St., 03143 Kyiv, Ukraine. Electronic address: v.kovalska@gmail.com.
authors.forename: Vladyslava B
authors.initials: VB
authors.lastname: Kovalska
authors.affiliation: Institute of Molecular Biology and Genetics NASU, 150 Zabolotnogo St., 03143 Kyiv, Ukraine.
authors.forename: Mykhaylo Yu
authors.initials: MY
authors.lastname: Losytskyy
authors.affiliation: Institute of General and Inorganic Chemistry NASU, 32/34 Palladin Av., 03680 Kyiv, Ukraine.
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Varzatskii
authors.affiliation: Institute of Physics NASU, 46 Nauky Av., 03680 Kyiv, Ukraine.
authors.forename: Vsevolod V
authors.initials: VV
authors.lastname: Cherepanov
authors.affiliation: Nesmeyanov Institute of Organoelement Compounds RAS, 28 Vavilova St., Moscow, Russia.
authors.forename: Yan Z
authors.initials: YZ
authors.lastname: Voloshin
authors.affiliation: Friedrich-Alexander-Universität Erlangen-Nürnberg, Department of Chemistry and Pharmacy, Organic Chemistry II, Henkestr. 42, Erlangen, Germany.
authors.forename: Andriy A
authors.initials: AA
authors.lastname: Mokhir
authors.affiliation: Institute of Molecular Biology and Genetics NASU, 150 Zabolotnogo St., 03143 Kyiv, Ukraine.
authors.forename: Sergiy M
authors.initials: SM
authors.lastname: Yarmoluk
authors.affiliation: Institute of General and Inorganic Chemistry NASU, 32/34 Palladin Av., 03680 Kyiv, Ukraine.
authors.forename: Sergiy V
authors.initials: SV
authors.lastname: Volkov
mesh_terms: D000682:Amyloid / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D005296:Ferrous Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000737:chemistry*; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D000682:Amyloid; D005296:Ferrous Compounds; D007328:Insulin; D047028:Macrocyclic Compounds
keywords: AFM; Amyloid fibrils; Fibrillization inhibition; Flow cytometry; Fluorescent detection; Iron(II) clathrochelates