The synthesis and evaluation of the antiproliferative activity of deacidified GEX1A analogues.
J Antibiot (Tokyo)
; 70(5): 675-679, 2017 May.
Article
em En
| MEDLINE
| ID: mdl-28096548
ABSTRACT
GEX1A/herboxidiene (1) is a natural product isolated from Streptomyces sp. and has been reported to target the pre-mRNA splicing process. Although 1 was shown to have antitumor activity in vivo, weight loss was observed in mice when 1 was consecutively administered. We assumed that the carboxylic acid moiety was one of the causes of this toxicity. In this study, a series of amide, carbamate and urea analogues of 1 were synthesized and their antiproliferative activity was evaluated in vitro. The synthesis of urea analogues featured Curtius rearrangement following amine treatment with the one-pot procedure from 1. Furthermore, a structure-activity relationship study of the urea analogues revealed that the pharmacologically preferable basic side chains were acceptable and that compound 9g was equipotent to parent 1. These basic urea analogues would be promising leads for the development of novel antitumor agents.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piranos
/
Ureia
/
Proliferação de Células
/
Álcoois Graxos
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
J Antibiot (Tokyo)
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Japão