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 (HL(1)), 9-bromo-6-N-(2-N',N'-dimethylaminoethylamino)-7,12-dihydroindolo[3,2-d][1]benzazepine (HL(2)), N-(9-bromo-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-yliden-N'-(1-pyridin-2-yl-methylidene)azine (HL(3)), or N-(9-bromo-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-yliden-N'-(1-pyridin-2-yl-ethylidene)azine (HL(4)) in methanol affords the novel copper(II) complexes [Cu(HL(1))Cl(2)] (1), [Cu(HL(2))Cl(2)] (2), [Cu(HL(3))Cl(2)] (3), [Cu(HL(4))Cl(2)] (4), and [Cu(L(4))(CH(3)COO)(CH(3)OH)] (5). The new ligands (HL(2) and HL(3)) and the complexes 1-5 were characterized by (1)H and (13)C NMR, IR and electronic absorption spectroscopy, ESI mass spectrometry, and X-ray crystallography. Two ligands, HL(1) and HL(2), 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 IC(50) values in the nanomolar range.
Primik
Michael F
MF
Institute of Inorganic Chemistry, University of Vienna, Austria.
Mühlgassner
Gerhard
G
Jakupec
Michael A
MA
Zava
Olivier
O
Dyson
Paul J
PJ
Arion
Vladimir B
VB
Keppler
Bernhard K
BK
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001552:Benzazepines / Q000737:chemistry; D002277:Carcinoma / Q000188:drug therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy; D003300:Copper / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D010051:Ovarian Neoplasms / Q000188:drug therapy
D000970:Antineoplastic Agents; D001552:Benzazepines; D009942:Organometallic Compounds; C547599:paullone; D003300:Copper