New propargyl thioquinolines--synthesis, antiproliferative activity in vitro and structure-activity relationships

The series of the propargyl thioquinolines has been prepared on the basis of the reaction of thioquinanthrene (1) (1,4-dithiino[2,3-c:5,6-c']-diquinoline) with sodium alkoxides. Some of these compounds have revealed good antiproliferative activity in vitro against the cells of human and murine cancer lines. 13C NMR spectra were measured for the studied compounds to examine the electronic properties-activity relationships. A regression study on 10 compounds showed a linear correlation of antiproliferative activity with electronic properties, expressed as the 13C NMR chemical shift for C-4 carbon atom (R2 = 0.97). It was found that compounds with chemical shift for C-4 value falling in the range of 135-140 ppm exhibited significant antiproliferative activity, while compounds which possess moderate or low activity are located in the range 140-165 ppm. This finding leads to the expectation that the antiproliferative activity of propargyl thioquinolines can be predicted using the 13C NMR chemical shift value of their C-4 carbon atom.