Docking and molecular biology studies of -anisidine-appended 1-hydroxy-2-acetonapthanone Schiff base lanthanum() complexes

A new series of lanthanum( iii ) complexes was synthesized using a p -anisidine-appended 1-hydroxy-2-acetonapthanone ( 3 ) Schiff base and characterized via spectroscopic methods. The ligand was synthesized via sonication and the crystalline product was characterized using X-ray crystallography. The genotoxicity of the compound was assessed primarily by the bacterial reverse mutation (Ames) test and the in vitro mammalian chromosome aberration test; in both cases, the samarium complex 5 was found to be non-mutagenic. The anti-tumor activity of complexes 4 , 5 , and 6 was assayed against HeLa tumor cells and screened using the MTT assay. The IC 50 value of complex 5 was found to be 34 ± 1.2 μg mL −1 and this compound exhibited superior activity towards the cells compared to 4 and 6 . These results were further confirmed by Hoechst 33258 staining and AO/EI dual staining, which indicated that the cells underwent an apoptosis mechanism in a dose-dependent manner. The apoptosis was further confirmed by the formation of ladders in the DNA fragmentation assay, and the western blot analysis of complex 5 suggested that the cells underwent the caspase-3-dependent pathway with PARP cleavage. Furthermore, the docking studies of complex 5 with HSA showed that it was situated in a hydrophilic cavity held by the electrostatic attraction of four hydrogen-bonding interactions. PDB ID: 1BNA binds with complex 5 via strong π-π stacking interactions, which facilitate binding with the major grooves of DNA strands. The above-mentioned results illustrate that for complex 5 , mitochondrion-mediated apoptosis occurs via caspase-3 activation. Complex 5 binds with DNA via intercalation because of S-phase cell cycle arrest in the HeLa cells. A new series of lanthanum( iii ) complexes was synthesized using a p -anisidine-appended 1-hydroxy-2-acetonapthanone ( 3 ) Schiff base and characterized via spectroscopic methods.