Synthesis and anticancer activity of 2-amino-8-chloro-5,5-dioxo[1,2,4]triazolo[2,3-b][1,4,2]benzodithiazine derivatives

Abstract

A new series of 1-(6-chloro-1,1-dioxo-1,4,2-benzodithiazin-3-yl)-4-arylsemicarbazides (4–16) were obtained. Intramolecular ring closure in semicarbazides 4–16 upon treatment with phosphorus oxychloride resulted in the formation of 2-amino-8-chloro-5,5-dioxo[1,2,4]triazolo[2,3-b][1,4,2]benzodithiazines 17–29 with potential antitumor activity. The structures of these compounds were confirmed on the basis of elemental analysis, spectral data and X-ray analysis. Compounds 17–29 were screened at the US National Cancer Institute (NCI) for their activities against a panel of 59 tumor cell lines, and relationships between structure and antitumor activity in vitro are discussed. The benzodithiazines 18, 19, 23, 28 and 29 were inactive, whereas the other compounds exhibited reasonable activity against numerous human tumor cell lines. The prominent compound 17 showed significant activity against the leukemia SR cell line (log GI50=−7.67, log TGI=−6.90 and log LC50=−4.77).