Discovery of N-arylcinnamamides as novel erythroblast enucleation inducers.
Bioorg Chem
; 128: 106105, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-36031698
ABSTRACT
Derivation of mature red blood cells (RBCs) from stem cells in vitro is a promising solution to the current shortage of blood supply, in which terminal enucleation is the rate-limiting step. Here we discovered two cinnamamides B8 and B16 showed potential activities of enhancing the enucleation of erythroblasts through the screening of "in-house" compound library. Subsequently, twenty-four N-arylcinnamamides were rationally designed and synthesized on the basis of the structure of B8 and B16, in which N-(9H-carbazol-2-yl)cinnamamide (KS-2) significantly elevated the percentage of reticulocytes in the cultured mouse fetal liver cells in vitro (relative enucleation = 2.43). The underlying mechanism of KS-2 in promoting mouse erythroid enucleation is accelerating the process of cell cycle exit via p53 activation in late stage erythrocytes. These results strongly suggest that compound KS-2 is worthy of further study as a potential erythrocyte enucleation inducer.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Eritroblastos
/
Eritropoese
Limite:
Animals
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China