Synthesis and biological evaluation of novel β-cyclodextrin-fluvastatin conjugates

Drugs that may regulate lipid metabolism and lower cholesterol, such as statins (drugs that reduce de novo cholesterol synthesis) or cyclodextrins (that promote cholesterol removal), are currently investigated as potential therapeutics for neuronal disorders like Alzheimer’s and Niemann Pick type C...

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Autores principales:	Mariacristina Nicolosi, Francesco Bellia, Maria Laura Giuffrida, Stefania Zimbone, Valentina Oliveri, Graziella Vecchio
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Antiaggregant Cholesterol Cyclodextrins Cytotoxicity Statin Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/5780f7be407d44f98a532a4621750f0e
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spelling	oai:doaj.org-article:5780f7be407d44f98a532a4621750f0e2021-11-12T04:32:13ZSynthesis and biological evaluation of novel β-cyclodextrin-fluvastatin conjugates2211-715610.1016/j.rechem.2021.100230https://doaj.org/article/5780f7be407d44f98a532a4621750f0e2021-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211715621001351https://doaj.org/toc/2211-7156Drugs that may regulate lipid metabolism and lower cholesterol, such as statins (drugs that reduce de novo cholesterol synthesis) or cyclodextrins (that promote cholesterol removal), are currently investigated as potential therapeutics for neuronal disorders like Alzheimer’s and Niemann Pick type C disease. Fluvastatin is a member of the statin class widely used in preventing heart diseases as it lowers cholesterol and other lipids. β-cyclodextrin derivatives can also act as cholesterol scavengers to promote cholesterol efflux from cells to extracellular acceptors.This context has inspired us to synthesize and characterize two new cyclodextrin-fluvastatin conjugates representing the first example of cyclodextrin conjugates of statins.We synthesized 3- and 6-functionalized β-cyclodextrin with fluvastatin through an amide bond. We studied the stability, cytotoxicity and protective activity in cells of the new derivatives. We observed that the Fluvastatin cyclodextrin conjugates are stable in plasma and mouse brain homogenates. Moreover, we found that the fluvastain derivatives are well tolerated by cultured neuron cells, and they completely rescue from cell death induced by Aβ oligomers. Overall, the fluvastain derivatives have potential as therapeutic agents in diseases related to cholesterol dyshomeostasis.Mariacristina NicolosiFrancesco BelliaMaria Laura GiuffridaStefania ZimboneValentina OliveriGraziella VecchioElsevierarticleAntiaggregantCholesterolCyclodextrinsCytotoxicityStatinChemistryQD1-999ENResults in Chemistry, Vol 3, Iss , Pp 100230- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Antiaggregant Cholesterol Cyclodextrins Cytotoxicity Statin Chemistry QD1-999
spellingShingle	Antiaggregant Cholesterol Cyclodextrins Cytotoxicity Statin Chemistry QD1-999 Mariacristina Nicolosi Francesco Bellia Maria Laura Giuffrida Stefania Zimbone Valentina Oliveri Graziella Vecchio Synthesis and biological evaluation of novel β-cyclodextrin-fluvastatin conjugates
description	Drugs that may regulate lipid metabolism and lower cholesterol, such as statins (drugs that reduce de novo cholesterol synthesis) or cyclodextrins (that promote cholesterol removal), are currently investigated as potential therapeutics for neuronal disorders like Alzheimer’s and Niemann Pick type C disease. Fluvastatin is a member of the statin class widely used in preventing heart diseases as it lowers cholesterol and other lipids. β-cyclodextrin derivatives can also act as cholesterol scavengers to promote cholesterol efflux from cells to extracellular acceptors.This context has inspired us to synthesize and characterize two new cyclodextrin-fluvastatin conjugates representing the first example of cyclodextrin conjugates of statins.We synthesized 3- and 6-functionalized β-cyclodextrin with fluvastatin through an amide bond. We studied the stability, cytotoxicity and protective activity in cells of the new derivatives. We observed that the Fluvastatin cyclodextrin conjugates are stable in plasma and mouse brain homogenates. Moreover, we found that the fluvastain derivatives are well tolerated by cultured neuron cells, and they completely rescue from cell death induced by Aβ oligomers. Overall, the fluvastain derivatives have potential as therapeutic agents in diseases related to cholesterol dyshomeostasis.
format	article
author	Mariacristina Nicolosi Francesco Bellia Maria Laura Giuffrida Stefania Zimbone Valentina Oliveri Graziella Vecchio
author_facet	Mariacristina Nicolosi Francesco Bellia Maria Laura Giuffrida Stefania Zimbone Valentina Oliveri Graziella Vecchio
author_sort	Mariacristina Nicolosi
title	Synthesis and biological evaluation of novel β-cyclodextrin-fluvastatin conjugates
title_short	Synthesis and biological evaluation of novel β-cyclodextrin-fluvastatin conjugates
title_full	Synthesis and biological evaluation of novel β-cyclodextrin-fluvastatin conjugates
title_fullStr	Synthesis and biological evaluation of novel β-cyclodextrin-fluvastatin conjugates
title_full_unstemmed	Synthesis and biological evaluation of novel β-cyclodextrin-fluvastatin conjugates
title_sort	synthesis and biological evaluation of novel β-cyclodextrin-fluvastatin conjugates
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/5780f7be407d44f98a532a4621750f0e
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Synthesis and biological evaluation of novel β-cyclodextrin-fluvastatin conjugates

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