Synthesis, Structure−Activity Relationships, and Antitumor Studies of 2-Benzoxazolyl Hydrazones Derived from Alpha-(N)-acyl Heteroaromatics
Recently we have described the antitumor activities of 2-benzoxazolylhydrazones derived from 2-formyl and 2-acetylpyridines. In search of a more efficacious analogue, compounds in which the 2-acetylpyridine moiety has been replaced by 2-acylpyridine and α-(N)-acetyldiazine/quinoline groups have been...
Gespeichert in:
Veröffentlicht in: | Journal of medicinal chemistry 2006-10, Vol.49 (21), p.6343-6350 |
---|---|
Hauptverfasser: | , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Recently we have described the antitumor activities of 2-benzoxazolylhydrazones derived from 2-formyl and 2-acetylpyridines. In search of a more efficacious analogue, compounds in which the 2-acetylpyridine moiety has been replaced by 2-acylpyridine and α-(N)-acetyldiazine/quinoline groups have been synthesized. The 2-acylpyridyl hydrazones inhibited in vitro cell proliferation in the nM range, whereas the hydrazones derived from the α-(N)-acetyldiazines/quinolines inhibited cell growth in the μM range. Compounds tested in the NCI-60 cell assay were effective inhibitors of leukemia, colon, and ovarian cancer cells. E -13k [N-benzoxazol-2-yl-N'-(1-isoquinolin-3-yl-ethylidene)-hydrazine] inhibited the proliferation of MCF-7 breast carcinoma cells more efficiently than nontransformed MCF-10A cells. It is not transported by P-glycoprotein and a weak MRP substrate. Increased concentrations of serum or α1-acid glycoprotein did not reduce the antiproliferative activity of the compound. In the in vivo hollow fiber assay, E -13k achieved a score of 24, with a net cell kill of OVCAR-3 (ovarian) and SF2-95 (CNS) tumor cells. |
---|---|
ISSN: | 0022-2623 1520-4804 |
DOI: | 10.1021/jm060232u |