Synthesis, structural and computational study, DNA binding and cytotoxic activity of Cu(II) complexes of 6- and 7-chloro-2-oxo-1,2-dihydroquinoline-3-carbaldehyde-2-furoyl-hydrazones

Abstract

Three new coordination complexes of Cu(II) ions made from two hydrazone ligands, 7-chloro-2-oxo-1,2-dihydro­ quinoline-3-arbaldehyde-2-furoyl-hydrazone (HL1) and 6-chloro-2-oxo-1,2-dihydroquinoline-3-carbaldehyde-2-furoyl-hydrazone (HL2) have been synthesized and fully characterized by spectroscopic techniques. Their crystal and molecular structures revealed istorted square pyramidal mononuclear complexes: [(L1)Cu(H2O)2](NO3)⋅3H2O, 1(NO3), [(L2)Cu(H2O)2](NO3)⋅2H2O⋅CH3OH, 2(NO3), nd [(L2)Cu(NO3)(CH3OH)]⋅2CH3OH, 3,comprising the ligand (L1 and L2) in tridentate fashion (ONO) with two water molecules in 1þ and 2þ, and a single methanol molecule and a nitrate ion in 3 in their espective copper coordination spheres. EPR spectra in frozen methanol revealed the occurrence of several species arising from different coordination environments. A detailed DFT investigation on the energetics of solvents exchange (H2O, MeOH, and DMSO) and simulation of the EPR parameters showed that the exchange processes occur easily in solution. The value gz indicated the occurrence of a dimeric aggregate for 2+. The new copper complexes exhibited a noticeable antiproliferative activity with IC50 values in the micromolar range against HCT-15, H157, BxPC3, PNS-1, and A431 cell lines and they were found to be 3-fold more effective than cisplatin against pancreatic PSN-1 cell lines. Cross-resistance tests on A2780 and LoVo cancer cell lines and the corresponding multidrug or oxaliplatin resistant sublines showed that complexes 1(NO3) and 2(NO3) were equally cytotoxic to sensitive and resistant cells, thus over­ coming multidrug and oxaliplatin resistance.