Choline kinase inhibitory effect and antiproliferative activity of new 1,1',1"-(benzene-1,3,5-triylmethylene)tris[4-[(disubstituted)amino]pyridinium] tribromides

Abstract

Four derivatives of 1,1'-(benzene-1,3-diylmethylene)bis[4-[(disubstituted)amino]-pyridinium] dibromides (2-5) and six derivatives of 1,1',1"-(benzene-1,3,5-triylmethylene)-tris[4-[(disubstituted)amino]pyridinium] tribromides (6-11) were synthesised and examined for their inhibition of human choline kinase (ChoK) and antiproliferative activities. The latter are more potent as ChoK inhibitors than the former, but the antiproliferative activities against the HT-29 cell line show the opposite tendency. The higher affinity of the trispyridinium compared with the bispyridinium ones may be due to direct binding of the third pyridinium group to ChoK or may arise from a reduction of the unfavourable entropy of binding via an increase of the 'local concentration' of pyridinium groups.