1. Academic Validation
  2. Synthesis, structure-activity relationships, and antitumor studies of 2-benzoxazolyl hydrazones derived from alpha-(N)-acyl heteroaromatics

Synthesis, structure-activity relationships, and antitumor studies of 2-benzoxazolyl hydrazones derived from alpha-(N)-acyl heteroaromatics

  • J Med Chem. 2006 Oct 19;49(21):6343-50. doi: 10.1021/jm060232u.
Johnny Easmon 1 Gerhard Pürstinger Katrin-Sofia Thies Gottfried Heinisch Johann Hofmann
Affiliations

Affiliation

  • 1 Institute of Pharmacy, Department of Pharmaceutical Chemistry, University of Innsbruck, Innrain 52a, A-6020 Innsbruck, Austria. johnny.easmon@uibk.ac.at
Abstract

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 In search of a more efficacious analogue, compounds in which the 2-acetylpyridine moiety has been replaced by 2-acylpyridine and alpha-(N)-acetyldiazine/quinoline groups have been synthesized.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 alpha-(N)-acetyldiazines/quinolines inhibited cell growth in the muM 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 alpha(1)-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.

Figures