Synthesis and electronic properties of ester substituted 1, 4-dicyanodibenzodioxins and evaluation of anti-proliferative activity of all isomeric 1, 2-, 2, 3- and 1, 4-dicyanodibenzodioxins against HeLa cell line. Issue 18 (15th September 2017)

• Record Type: Journal Article
• Authors: Banerjee, Subhadeep; Chattopadhyay, Anjan; Fernandes, Joseph R.D.; Banerjee, Arnab; Phadte, Apeksha Ashok; Savardekar, Akanksha Vinod; Singh, Keisham Sarjit
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 18(2017)
• Page Start: 4280
• Page End: 4284
• Publication Date: 2017-09-15
• Subjects: Dicyanodibenzodioxin -- Anti-tumor activity -- HeLa cell line -- ROS -- HEK 293 cell line; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.08.042
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 1, 4-Dicyanodibenzodioxins bearing carboxy methyl ester groups were synthesized using our established one-step SNAr coupling reaction between ortho- and meta -ester substituted catechols and perfluorinated terephthalonitrile. These are the first examples of 1, 4-dicyanodibenzodioxins substituted at both the benzene moieties. Optical spectra were similar to the earlier examples reported, with a marginal blue shift for the ester dibenzodioxins. Theoretical analysis of the molecular orbitals reveals modest destabilization of the frontier molecular orbitals of one carboxy methyl ester isomer over the other and overall higher HOMO-LUMO gap for both isomers when compared to the earlier published 1, 4-dicyanodibenzodioxins. In vitro cytotoxicity against human cervical cancer HeLa cell line was evaluated for these two compounds and all other previously published dibenzodioxins from our laboratory (1, 4-dicyano, 1, 2-dicyano and 2, 3-dicyano variants). A number of derivatives showed anti-tumor activity in μM ranges and also exhibited no cytotoxicity against normal HEK 293 cell line. Mechanistic investigation of cell death pathways indicated high levels of reactive oxygen species (ROS) in the dibenzodioxin treated tumor cell lines along with cellular nuclear fragmentation, both of which are markers of the apoptotic cell death pathway.