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

Abstract

Four Schiff bases derived from 7-hydrazin-yl-5,8-dihydroindolo[2,3-d][2]benzazepin-(6H)-one and its bromo-substituted analogue (HL¹–HL⁴) and four copper(II) complexes 1–4 have been synthesised and fully characterised by standard spectroscopic methods (¹H and ¹³C 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 IC₅₀ values in the low micromolar to nanomolar concentration range.