Strong in vitro anticancer activity of copper(ii) and zinc(ii) complexes containing naturally occurring lapachol:...

Copper(ii) and zinc(ii) complexes with lapachol (HLap) of the composition [M(Lap)₂(N-N)] and [Cu(Lap)(H₂O)(terpy)]NO₃ (4), where M = Cu (1-3) or Zn (for 5-7), and N-N stands for bathophenanthroline (1 and 5), 5-methyl-1,10-phenanthroline (2 and 6), 2,2'-bipyridine (3), 2,2';6',2''-terpyridine (terpy, 4) and 1,10-phenanthroline (7), were synthesised and characterised. Complexes 1-5 revealed strong in vitro antiproliferative effects against A2780, A2780R, MCF-7, PC-3, A549 and HOS human cancer lines and MRC-5 normal cells, with IC₅₀ values above 0.5 μM, and reasonable selectivity index (SI), with SI > 3.8 for IC₅₀(MRC-5)/IC₅₀(A2780). Considerable time-dependent cytotoxicity in A2780 cells was observed for complexes 6 and 7, with IC₅₀ > 50 μM (24 h) to ca. 4 μM (48 h). Cellular effects of complexes 1, 5 and 7 in A2780 cells were investigated by flow cytometry revealing that the most cytotoxic complexes (1 and 5) significantly perturbed the mitochondrial membrane potential and the interaction with mitochondrial metabolism followed by the triggering of the intracellular pathway of apoptosis.