Biosynthesis, synthesis, and biological activities of pyrrolobenzodiazepines.
Med Res Rev
; 32(2): 254-93, 2012 Mar.
Article
em En
| MEDLINE
| ID: mdl-20544978
ABSTRACT
Pyrrolobenzodiazepines (PBDs) are sequence selective DNA alkylating agents with remarkable antineoplastic activity. They are either naturally produced by actinomycetes or synthetically produced. The remarkable broad spectrum of activities of the naturally produced PBDs encouraged the synthesis of several PBDs, including dimeric and hybrid PBDs yielding to an improvement in the DNA-binding sequence specificity and in the potency of this class of compounds. However, limitation in the chemical synthesis prevented the testing of one of the most potent PBDs, sibiromycin, a naturally produced glycosylated PBDs. Only recently, the biosynthetic gene clusters for PBDs have been identified opening the doors to the production of glycosylated PBDs by mutasynthesis and biosynthetic engineering. This review describes the recent studies on the biosynthesis of naturally produced pyrrolobenzodiazepines. In addition, it provides an overview on the isolation and characterization of naturally produced PBDs, chemical synthesis of PBDs, mechanism of DNA alkylation, and DNA-binding affinity and cytotoxic properties of both naturally produced and synthetic pyrrolobenzodiazepines.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirróis
/
Benzodiazepinas
/
DNA
/
Actinobacteria
/
Antineoplásicos Alquilantes
Idioma:
En
Revista:
Med Res Rev
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos