Novel Disulfiram Derivatives as ALDH1a1-Selective Inhibitors.
Molecules
; 27(2)2022 Jan 12.
Article
em En
| MEDLINE
| ID: mdl-35056791
ABSTRACT
Aldehyde dehydrogenase-1a1 (ALDH1a1), the enzyme responsible for the oxidation of retinal into retinoic acid, represents a key therapeutic target for the treatment of debilitating disorders such as cancer, obesity, and inflammation. Drugs that can inhibit ALDH1a1 include disulfiram, an FDA-approved drug to treat chronic alcoholism. Disulfiram, by carbamylation of the catalytic cysteines, irreversibly inhibits ALDH1a1 and ALDH2. The latter is the isozyme responsible for important physiological processes such as the second stage of alcohol metabolism. Given the fact that ALDH1a1 has a larger substrate tunnel than that in ALDH2, replacing disulfiram ethyl groups with larger motifs will yield selective ALDH1a1 inhibitors. We report herein the synthesis of new inhibitors of ALDH1a1 where (hetero)aromatic rings were introduced into the structure of disulfiram. Most of the developed compounds retained the anti-ALDH1a1 activity of disulfiram; however, they were completely devoid of inhibitory activity against ALDH2.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Dissulfiram
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Retinal Desidrogenase
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Inibidores de Acetaldeído Desidrogenases
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Família Aldeído Desidrogenase 1
Limite:
Humans
Idioma:
En
Revista:
Molecules
Assunto da revista:
BIOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Arábia Saudita