title: Enhanced antiamyloidal activity of hydroxy cinnamic acids by enzymatic esterification with alkyl alcohols.
abstract: Lipophilic derivatives of hydroxyl cinnamic acids (HCAs) including caffeic acid (CA), ferulic acid, sinapic acid (SA), and chlorogenic acid were synthesized by esterification with butanol, octanol, or hexadecanol catalyzed by the lipase from Candida antarctica to investigate the effect of lipophilicity on their antiamyloidal activity assessed by the inhibitory activities toward fibrillization of amyloid β (Aβ) peptide. Among them, CA showed the highest activity at 50 μM, reducing the amyloid fibril formation of Aβ to 34.4 ± 6.8%. The antiamyloidal effects of HCAs were enhanced by esterification with alkyl alcohols, and the longer alkyl chain tended to be more effective except for SA. Aβ fibril formation was suppressed by the hexadecyl ester of CA, which was reduced to 8.8 ± 2.3%. In contrast, those of octyl and butyl esters were 19.3 ± 2.3% and 41.6 ± 6.1%, respectively. These results show that lipophilicity plays an important role in the antiamyloidal activities of esterified phenolic compounds.
authors.affiliation: Department of Bioscience and Biotechnology, Shinshu University, Minamiminowa, Nagano, Japan.
authors.forename: Hazuki
authors.initials: H
authors.lastname: Kondo
authors.affiliation: Department of Bioscience and Biotechnology, Shinshu University, Minamiminowa, Nagano, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Sugiyama
authors.affiliation: Department of Bioscience and Biotechnology, Shinshu University, Minamiminowa, Nagano, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Katayama
authors.affiliation: Department of Bioscience and Biotechnology, Shinshu University, Minamiminowa, Nagano, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D000438:Alcohols / Q000737:chemistry / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors*; D055162:Biocatalysis; D002175:Candida / Q000201:enzymology; D002934:Cinnamates / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D008049:Lipase / Q000378:metabolism*; D015394:Molecular Structure
chemical_list: D000438:Alcohols; D016229:Amyloid beta-Peptides; D002934:Cinnamates; C029010:cinnamic acid; D008049:Lipase
keywords: amyloid β; antiamyloidal activity; esterification; hydroxyl cinnamic acids; lipase; lipophilicity