Fluorinated Molecules and Nanotechnology: Future ‘Avengers’ against the Alzheimer’s Disease?

Abstract

Alzheimer’s disease (AD) is a serious health concern, affecting millions of people globally, which leads to cognitive impairment, dementia, and inevitable death. There is still no medically accepted treatment for AD. Developing therapeutic treatments for AD is an overwhelming challenge in the medicinal field, as the exact mechanics underlying its devastating symptoms is still not completely understood. Rather than the unknown mechanism of the disease, one of the limiting factors in developing new drugs for AD is the blood–brain barrier (BBB). A combination of nanotechnology with fluorinated molecules is proposed as a promising therapeutic treatment to meet the desired pharmacokinetic/physiochemical properties for crossing the BBB passage. This paper reviews the research conducted on fluorine-containing compounds and fluorinated nanoparticles (NPs) that have been designed and tested for the inhibition of amyloid-beta (Aβ) peptide aggregation. Additionally, this study summarizes fluorinated molecules and NPs as promising agents and further future work is encouraged to be effective for the treatment of AD.

Perfluorocarbons in Chemical Biology

“…Perfluorination could be a tool for subcellular localization of proteins and increase membrane affinity as palmitoylation does [161,162] or to help therapeutic biomolecules and diagnostics permeate the hydrophobic blood-brain barrier. [18,[163][164][165][166] Beyond directing events in cellulo and in vivo, perfluorination could provide exciting opportunities for interfacing biological systems with unnatural hydrophobic materials.…”

“…Looking forward, the significant work towards incorporating perfluorinated groups into proteins, peptides, carbohydrates, and lipids should facilitate new tools for manipulating and studying biological systems in research laboratories and in clinical settings. Perfluorination could be a tool for subcellular localization of proteins and increase membrane affinity as palmitoylation does [161,162] or to help therapeutic biomolecules and diagnostics permeate the hydrophobic blood‐brain barrier [18,163–166] . Beyond directing events in cellulo and in vivo, perfluorination could provide exciting opportunities for interfacing biological systems with unnatural hydrophobic materials.…”

Vitamin B12 Inhibits Aβ Fibrillation and Disaggregates Preformed Fibrils in the Presence of Synthetic Neuronal Membranes

“…Dementia is characterized by the deterioration of specific areas of the brain, that causes loss of memory and inevitable cognitive impairment. Alzheimer’s disease (AD) is the most common cause of dementia, accounting with about 70% of dementia cases worldwide . Unfortunately, there is no treatment available to cure AD or delay its progression, with the current medications just aiming to control the symptoms .…”

“…Alzheimer's disease (AD) is the most common cause of dementia, accounting with about 70% of dementia cases worldwide. 2 Unfortunately, there is no treatment available to cure AD or delay its progression, with the current medications just aiming to control the symptoms. 3 However, efforts have been made to find new strategies to treat AD.…”

On the Question of Zwitterionic Intermediates in the [3 + 2] Cycloaddition Reactions between C-arylnitrones and Perfluoro 2-Methylpent-2-ene

“…The specific properties of fluoroorganic compounds, such as pKa, steric effects, lipophilicity, inductive effects, hydrogen bonding, and isosterism, provide a wide range of applications in medicinal chemistry [ 3 ]. In particular, the C-F- moiety is a key element in thymidylate synthase inhibitors (such as galocitabine, emitefur, ftorafur, and fluorocytosine), topoisomerase inhibitors (such as clofarabine and fluodarabine), microtubule-stabilizing agents (such as paclitaxel), multi-drug efflux protein resistance (raloxifene and zosuguidar), protein kinase inhibitors (gefitinib), anti-androgens (nilitamide, fluramide), non-steroidal anti-inflammatory drugs (colecoxib and diflunisal) [ 4 ], and antimicrobial agents [ 5 ], as well as drugs devoted to Alzheimer’s disease [ 6 ]. Some fluoroorganic compounds play an effective xenobiotic function in peptide backbone modification [ 7 ].…”