Source: Bioorganic & Medicinal Chemistry Letters (Print), v. 24, p. 934-939, 2014.
Publisher: Elsevier
Abstract
A series of forty-seven quinoxaline derivatives, 2-(XYZC
6H
2CH

N–NH)-quinoxalines,
1, have been synthesized and evaluated for their activity against four cancer cell lines: potent cytotoxicities were found (IC
50 ranging from 0.316 to 15.749 μM). The structure–activity relationship (SAR) analysis indicated that the number, the positions and the type of substituents attached to the aromatic ring are critical for biological activity. The activities do not depend on the electronic effects of the substituents nor on the lypophilicities of the molecules. A common feature of active compounds is an
ortho-hydroxy group in the phenyl ring. A potential role of these
ortho-hydroxy derivatives is as
N,
N,
O-tridentate ligands complexing with a vital metal, such as iron, and thereby preventing proliferation of cells. The most active compound was (
1: X,Y = 2,3-(OH)
2, Z = H), which displayed a potent cytotoxicity comparable to that of the reference drug doxorubicin.
Keywords: Antitumor activity, quinoxaline, hydrazone, drugs
Document Type: Research Article
DOI: http://dx.doi.org/10.1016/j.bmcl.2013.12.074
Publication date: 1 de Fevereiro de 2014