Novel latonduine derived proligands and their copper() complexes show cytotoxicity in the nanomolar range in human colon adenocarcinoma cells and cancer selectivity

Four Schiff bases derived from 7-hydrazin-yl-5,8-dihydroindolo[2,3- d ][2]benzazepin-(6 H )-one and its bromo-substituted analogue ( HL 1 -HL 4 ) and four copper( ii ) complexes 1-4 have been synthesised and fully characterised by standard spectroscopic methods ( 1 H and 13 C NMR, UV-vis), ESI mass spectrometry, single crystal X-ray diffraction and spectroelectrochemistry. In addition, two previously reported complexes with paullone ligands 5 and 6 were prepared and studied for comparison reasons. The Cu II ion in 1-4 is five-coordinate and adopts a square-pyramidal or slightly distorted square-pyramidal coordination geometry. The ligands HL 1-4 act as tridentate, the other two coordination places are occupied by two chlorido co-ligands. The organic ligands in 2 and 3 are bound tighter to copper( ii ) when compared to related paullone ligands in 5 and 6 . The new compounds show very strong cytotoxic activity against human colon adenocarcinoma doxorubicin-sensitive Colo 205 and multidrug resistant Colo 320 cancer cell lines with IC 50 values in the low micromolar to nanomolar concentration range. The copper( ii ) complexes with latonduine derivatives are superior to those with isomeric paullone modified ligands.