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

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          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.

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          Fluorine in medicinal chemistry.

          It has become evident that fluorinated compounds have a remarkable record in medicinal chemistry and will play a continuing role in providing lead compounds for therapeutic applications. This tutorial review provides a sampling of renowned fluorinated drugs and their mode of action with a discussion clarifying the role and impact of fluorine substitution on drug potency.
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            Fluorine in pharmaceuticals: looking beyond intuition.

            Fluorine substituents have become a widespread and important drug component, their introduction facilitated by the development of safe and selective fluorinating agents. Organofluorine affects nearly all physical and adsorption, distribution, metabolism, and excretion properties of a lead compound. Its inductive effects are relatively well understood, enhancing bioavailability, for example, by reducing the basicity of neighboring amines. In contrast, exploration of the specific influence of carbon-fluorine single bonds on docking interactions, whether through direct contact with the protein or through stereoelectronic effects on molecular conformation of the drug, has only recently begun. Here, we review experimental progress in this vein and add complementary analysis based on comprehensive searches in the Cambridge Structural Database and the Protein Data Bank.
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              The many roles for fluorine in medicinal chemistry.

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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                23 April 2020
                April 2020
                : 21
                : 8
                : 2989
                Affiliations
                LEPABE, Department of Chemical Engineering, Faculty of Engineering of the University of Porto, s/n, R. Dr. Roberto Frias, 4200-465 Porto, Portugal; meghna.dabur@ 123456outlook.com
                Author notes
                [* ]Correspondence: joana.loureiro@ 123456fe.up.pt (J.A.L.); mcsp@ 123456fe.up.pt (M.C.P.)
                Author information
                https://orcid.org/0000-0003-3226-0117
                https://orcid.org/0000-0002-9841-3967
                https://orcid.org/0000-0001-8505-3432
                Article
                ijms-21-02989
                10.3390/ijms21082989
                7216102
                32340267
                04f60378-41ea-4a01-b5eb-3cb4d1da65d9
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 12 April 2020
                : 21 April 2020
                Categories
                Review

                Molecular biology
                amyloid-beta peptide,bace inhibitors,amyloid-beta aggregation,fluorine,nanoparticles

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