Design, synthesis and biological evaluation of novel tetralone/indanone containing thiosemicarbazone derivatives with selective COX-2 inhibition as anticancer agents

A series of novel tetralone/indanone moiety-bearing thiosemicarbazone derivatives were synthesized and evaluated for their biological activities. The structural elucidations of the compounds were performed by IR spectroscopy, 1H-NMR, 13C-NMR, and elemental analysis. Cytotoxic activity studies against A549 lung adenocarcinoma cells, CCD-19Lu fibroblast cell line were performed. Furthermore, flow cytometric analyses of mitochondrial membrane potential (JC1), caspase 3 activities, cytotoxic activities against HEK 293 immortalized human embriyonic kidney cell lines and MCF7 human breast cancer cell lines, COX-1 and COX-2 enzyme inhibition activities were evaluated for 2e, 2i, 3c, and 3d. In addition to the in vitro analysis, molecular docking studies were employed to explore the possible binding interactions of the title compounds with COX-1 (PDB ID: 3KK6) and COX-2 (PDB ID: 3LN1). Structure-activity relationships, as well as virtual ADME studies, were carried out and a relationship between the biological, electronic, and physicochemical qualifications of the target compounds was determined. Consequently, these derivatives present a leading structure for future drug development due to their straightforward synthesis and relevant bioactivity.