Multiple sclerosis (MS) is a complex inflammatory, degenerative, and demyelinating disease of the central nervous system. Although treatments exist, MS cannot be cured by available drugs, which primarily target neuroinflammation. Thus, it is feasible that a well concerted polypharmacological approach able to act at multiple points within the intricate network of inflammation, neurodegeneration, and demyelination/remyelination pathways would succeed where other drugs have failed. Starting from reported beneficial effects of α-linolenic acid (ALA) and valproic acid (VPA) in MS, and by applying a rational strategy, we developed a small set of codrugs obtained by conjugating VPA and ALA through proper linkers. A cellular profiling identified 1 as a polypharmacological tool able not only to modulate microglia polarization, but also to counteract neurodegeneration and demyelination and induce oligodendrocyte precursor cell differentiation, by acting on multiple biochemical and epigenetic pathways.
α-linolenic acid-valproic acid conjugates: Toward single-molecule polypharmacology for multiple sclerosis / Rossi M.; Petralla S.; Protti M.; Baiula M.; Kobrlova T.; Soukup O.; Spampinato S.M.; Mercolini L.; Monti B.; Bolognesi M.L.. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - ELETTRONICO. - 11:12(2020), pp. 2406-2413-2413. [10.1021/acsmedchemlett.0c00375]
α-linolenic acid-valproic acid conjugates: Toward single-molecule polypharmacology for multiple sclerosis
Rossi M.;Petralla S.;Protti M.;Baiula M.;Spampinato S. M.;Mercolini L.;Monti B.;Bolognesi M. L.
2020
Abstract
Multiple sclerosis (MS) is a complex inflammatory, degenerative, and demyelinating disease of the central nervous system. Although treatments exist, MS cannot be cured by available drugs, which primarily target neuroinflammation. Thus, it is feasible that a well concerted polypharmacological approach able to act at multiple points within the intricate network of inflammation, neurodegeneration, and demyelination/remyelination pathways would succeed where other drugs have failed. Starting from reported beneficial effects of α-linolenic acid (ALA) and valproic acid (VPA) in MS, and by applying a rational strategy, we developed a small set of codrugs obtained by conjugating VPA and ALA through proper linkers. A cellular profiling identified 1 as a polypharmacological tool able not only to modulate microglia polarization, but also to counteract neurodegeneration and demyelination and induce oligodendrocyte precursor cell differentiation, by acting on multiple biochemical and epigenetic pathways.File | Dimensione | Formato | |
---|---|---|---|
acsmedchemlett.0c00375.pdf
accesso aperto
Tipo:
Versione (PDF) editoriale
Licenza:
Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY)
Dimensione
3.96 MB
Formato
Adobe PDF
|
3.96 MB | Adobe PDF | Visualizza/Apri |
ml0c00375_si_001.pdf
accesso aperto
Tipo:
File Supplementare
Licenza:
Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY)
Dimensione
636.62 kB
Formato
Adobe PDF
|
636.62 kB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.