A Half-Sandwich Os(II) Glucoconjugated NHC Complex as a Modulator of Amyloid Aggregation DOI Creative Commons

Daniele Florio,

Alfonso Annunziata, Valeria Panzetta

et al.

Inorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Herein, the effects of a novel half-sandwich Os(II) complex on aggregation an amyloid model system, derived from C-terminal domain nucleophosmin 1 protein (NPM1264–277), were investigated. The thioflavin T (ThT) binding assay revealed that [(η6-toluene)Os(NHCglu)Cl2] (where NHCglu is N-heterocyclic carbene ligand 1-methyl-3-{2,3,4,6-tetra-O-acetyl-1-glucosyl}imidazol-2-ylidene), hence named Os-Tolu, was able to repress in dose-dependent way. Conformational studies through circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopies clearly indicated this inhibitory effect occurred stabilization α-helical structures monomeric NPM1264–277, thus hampering self-recognition. Electrospray ionization mass spectrometry (ESI-MS) evidenced, formation coordination adducts, direct interactions peptide with Os-glucoconjugate that, turn, promote chemical modifications sequence further disfavoring self-assembly process. Noticeably, presence Os-Tolu completely repressed fibers scanning electron microscopy (SEM) analysis induced slight rescue cell viability, contrast its reduction caused by human SH-SY5Y neuroblastoma cells. These data strongly support hypothesis expanding use osmium-based agents neurodegenerative diseases, positioning them as potential neurodrugs.

Language: Английский

Advances in the Potential of Quinoline‐Derived Metal Complexes as Antimalarial Agents: A Review DOI Open Access
Carla Peron, Raoni S. B. Gonçalves, Sidnei Moura

et al.

Applied Organometallic Chemistry, Journal Year: 2025, Volume and Issue: 39(3)

Published: Feb. 11, 2025

ABSTRACT Quinolines obtained from native trees of South and Central America, the genus Cinchona , have been used since 17th century for treatment malaria. However, it was only in 1820 that quinine had its structure elucidated, subsequently, during 20th century, several synthetic derivatives were produced with superior activities. In parallel, search synthesis metal complex compounds malaria dates 1994, development ferroquine, an iron derived chloroquine, developed by Biot collaborators at Lille University. After, there are complexes synthesized various metals, such as ruthenium, gold, iridium, platinum, over last 30 years, which aims this review. This review identified 84 quinoline–metal reported across 25 studies, gold (Complex 63) showing significant potency against FcBI strain (IC 50 10 nM), outperforming chloroquine (CQ, indicating coordination enhances drug's action. The ruthenium 03) exhibited activity PFB but less effective than CQ 22.5 vs. 8.2 nM). Other complexes, Au(III) 61), Ir(I) 52), Ir(II) 50), also demonstrated promising results varying effectiveness different strains. Structural features, including linear geometry Au(I) square planar or piano stool geometries Ru(II) Ir play crucial roles influencing their biological activity. These findings highlight potential improving antimalarial efficacy.

Language: Английский

Citations

0
A Half-Sandwich Os(II) Glucoconjugated NHC Complex as a Modulator of Amyloid Aggregation DOI Creative Commons

Daniele Florio,

Alfonso Annunziata, Valeria Panzetta

et al.

Inorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Herein, the effects of a novel half-sandwich Os(II) complex on aggregation an amyloid model system, derived from C-terminal domain nucleophosmin 1 protein (NPM1264–277), were investigated. The thioflavin T (ThT) binding assay revealed that [(η6-toluene)Os(NHCglu)Cl2] (where NHCglu is N-heterocyclic carbene ligand 1-methyl-3-{2,3,4,6-tetra-O-acetyl-1-glucosyl}imidazol-2-ylidene), hence named Os-Tolu, was able to repress in dose-dependent way. Conformational studies through circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopies clearly indicated this inhibitory effect occurred stabilization α-helical structures monomeric NPM1264–277, thus hampering self-recognition. Electrospray ionization mass spectrometry (ESI-MS) evidenced, formation coordination adducts, direct interactions peptide with Os-glucoconjugate that, turn, promote chemical modifications sequence further disfavoring self-assembly process. Noticeably, presence Os-Tolu completely repressed fibers scanning electron microscopy (SEM) analysis induced slight rescue cell viability, contrast its reduction caused by human SH-SY5Y neuroblastoma cells. These data strongly support hypothesis expanding use osmium-based agents neurodegenerative diseases, positioning them as potential neurodrugs.

Language: Английский

Citations

0