Staurosporine Derivatives Generated by Pathway Engineering in a Heterologous Host and Their Cytotoxic Selectivity.
J Nat Prod
; 81(8): 1745-1751, 2018 08 24.
Article
em En
| MEDLINE
| ID: mdl-30106291
ABSTRACT
Two new staurosporine derivatives, staurosporines M1 and M2 (4 and 5), in addition to five previously reported metabolites (1-3, 6, and 7), were generated by the heterologous expression of engineered spc gene clusters in Streptomyces coelicolor M1146. The structures of these derivatives were determined by a combination of spectroscopic methods and CD measurement. Compounds 1, 2, 4, and 5 showed effective activities against three tumor cell lines (HCT-116, K562, and Huh 7.5), and 3 was active against HCT-116 and K562 cells. In addition, compounds 3 and 5 showed undetectable toxicity up to 100 µM toward the normal hepatic cell line LO2. Based on the IC50 values, their structure and activity relationships are discussed.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estaurosporina
/
Antibióticos Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
J Nat Prod
Ano de publicação:
2018
Tipo de documento:
Article