The role of oxidative stress in 63 T-induced cytotoxicity against human lung cancer and normal lung fibroblast cell lines.

It has been shown previously that molecules built on benzanilide and thiobenzanilide scaffolds possess differential biological properties including selective anticancer activity. In our previous study, we examined the cytotoxic activity and mechanism of action of the thiobenzanilide derivative N,N'-(1,2-phenylene)bis3,4,5-trifluorobenzothioamide (63 T) as a potential chemotherapeutic compound in an experimental model employing A549 lung adenocarcinoma cells and CCD39Lu non-tumorigenic lung fibroblasts. Since the results suggested oxidative stress as a co-existing mechanism of the cytotoxic effect exerted by 63 T on tested cells, studies involving the analysis of reactive oxygen species (ROS) generation and markers of oxidative stress in cells incubated with 63 T were carried out.

Selective anticancer activity of the novel thiobenzanilide 63T against human lung adenocarcinoma cells.

Previously, it has been reported that molecules built on the benzanilide and thiobenzanilide scaffold are the promising groups of compounds with several biological activities including antifungal, antimycotic, antibacterial, spasmolytic, and anticancer ones. In this study the mechanism of action of one selected thiobenzanilide derivative N,N'-(1,2-phenylene)bis3,4,5-trifluorobenzothioamide (63T) with strongest cytotoxic activity has been investigated for the first time in human lung adenocarcinoma (A549) and normal lung derived fibroblast (CCD39Lu) in a cell culture model. The results demonstrated, that 63T can be considered a selective anticancer compound.

Novel Promising Estrogenic Receptor Modulators: Cytotoxic and Estrogenic Activity of Benzanilides and Dithiobenzanilides.

The cytotoxicity of 27 benzanilides and dithiobenzanilides built on a stilbene scaffold and possessing various functional groups in aromatic rings previously described for their spasmolytic properties was assayed on three human cancer cell lines (A549 -lung adenocarcinoma, MCF-7 estrogen dependent breast adenocarcinoma and MDA-MB-231 estrogen independent breast adenocarcinoma) and 2 non-tumorigenic cell lines (CCD39Lu-lung fibroblasts, MCF-12A - breast epithelial). Three compounds (6, 15 and 18) showed selective antiproliferative activity against estrogen dependent MCF-7 cancer cells and their estrogenic activity was further confirmed in MCF-7 transfected with an estrogen receptor reporter plasmid and in HEK239 cells over-expressing the estrogen receptor alpha (ERα). Compound 18 is especially interesting as a potential candidate for therapy since it is highly toxic and selective towards estrogen dependent MCF7 cell lines (IC50 = 5.

A journey from benzanilides to dithiobenzanilides: Synthesis of selective spasmolytic compounds.

A series of dithiobenzanilide derivatives was synthesized and each compound was evaluated for its ability to reduce KCl-induced contractions of smooth muscle preparations of the guinea pig. Starting from a recent publication describing benzanilide derivatives as antispasmodic agents, structure-activity guided synthesis was performed to obtain compounds with improved spasmolytic activity. First, compounds with two amide bonds were designed and second, both amide oxygens were replaced by two sp² sulfur atoms resulting in dithiobenzanilide derivatives.