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Asymmetric Synthesis of Saturated and Unsaturated Hydroxy Fatty Acids (HFAs) and Study of Their Antiproliferative Activity.
Mountanea, Olga G; Mantzourani, Christiana; Gkikas, Dimitrios; Politis, Panagiotis K; Kokotos, George.
Afiliación
  • Mountanea OG; Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece.
  • Mantzourani C; Center of Excellence for Drug Design and Discovery, National and Kapodistrian University of Athens, 15771 Athens, Greece.
  • Gkikas D; Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece.
  • Politis PK; Center of Excellence for Drug Design and Discovery, National and Kapodistrian University of Athens, 15771 Athens, Greece.
  • Kokotos G; Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, 4 Soranou Efesiou Str., 11527 Athens, Greece.
Biomolecules ; 14(1)2024 Jan 15.
Article en En | MEDLINE | ID: mdl-38254710
ABSTRACT
Hydroxy fatty acids (HFAs) constitute a class of lipids, distinguished by the presence of a hydroxyl on a long aliphatic chain. This study aims to expand our insights into HFA bioactivities, while also introducing new methods for asymmetrically synthesizing unsaturated and saturated HFAs. Simultaneously, a procedure previously established by us was adapted to generate new HFA regioisomers. An organocatalytic step was employed for the synthesis of chiral terminal epoxides, which either by alkynylation or by Grignard reagents resulted in unsaturated or saturated chiral secondary alcohols and, ultimately, HFAs. 7-(S)-Hydroxyoleic acid (7SHOA), 7-(S)-hydroxypalmitoleic acid (7SHPOA) and 7-(R)- and (S)-hydroxymargaric acids (7HMAs) were synthesized for the first time and, together with regioisomers of (R)- and (S)-hydroxypalmitic acids (HPAs) and hydroxystearic acids (HSAs), whose biological activity has not been tested so far, were studied for their antiproliferative activities. The unsaturation of the long chain, as well as an odd-numbered (C17) fatty acid chain, led to reduced activity, while the new 6-(S)-HPA regioisomer was identified as exhibiting potent antiproliferative activity in A549 cells. 6SHPA induced acetylation of histone 3 in A549 cells, without affecting acetylated α-tubulin levels, suggesting the selective inhibition of histone deacetylase (HDAC) class I enzymes, and was found to inhibit signal transducer and activator of transcription 3 (STAT3) expression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácidos Grasos / Ácidos Grasos Insaturados Límite: Humans Idioma: En Revista: Biomolecules Año: 2024 Tipo del documento: Article País de afiliación: Grecia Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácidos Grasos / Ácidos Grasos Insaturados Límite: Humans Idioma: En Revista: Biomolecules Año: 2024 Tipo del documento: Article País de afiliación: Grecia Pais de publicación: Suiza