Highly Cytotoxic Copper(II) Complexes with Modified Paullone Ligands

The reaction of copper(II) chloride or copper(II) acetate with 6-N-(2-N′,N′-dimethylaminoethylamino)-7,12-dihydroindolo-[3,2-d][1]benzazepine (HL1), 9-bromo-6-N-(2-N′,N′-dimethylaminoethylamino)-7,12-dihydroindolo[3,2-d][1]benzazepine (HL2), N-(9-bromo-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-yliden-N′-(1-pyridin-2-yl-methylidene)azine (HL3), or N-(9-bromo-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-yliden-N′-(1-pyridin-2-yl-ethylidene)azine (HL4) in methanol affords the novel copper(II) complexes [Cu(HL1)Cl2] (1), [Cu(HL2)Cl2] (2), [Cu(HL3)Cl2] (3), [Cu(HL4)Cl2] (4), and [Cu(L4)(CH3COO)(CH3OH)] (5). The new ligands (HL2 and HL3) and the complexes 1−5 were characterized by 1H and 13C NMR, IR and electronic absorption spectroscopy, ESI mass spectrometry, and X-ray crystallography. Two ligands, HL1 and HL2, and complexes 1−4 were tested for cytotoxicity in three human cancer cell lines, namely, CH1 (ovarian carcinoma), A549 (non-small cell lung cancer), and SW480 (colon carcinoma). Additionally, complexes 1, 2, and 4 were assayed in an isogenic pair of ovarian cancer cell lines, one being sensitive to cisplatin (A2780) and the other having acquired cisplatin resistance (A2780cisR). All of the compounds evaluated are cytotoxic, with complexes 3 and 4 exhibiting IC50 values in the nanomolar range.