Docking andin vitromolecular biology studies ofp-anisidine-appended 1-hydroxy-2-acetonapthanone Schiff base lanthanum(iii) complexes

Document Type

Article

Publication Title

RSC Advances

Abstract

A new series of lanthanum(iii) complexes was synthesized using ap-anisidine-appended 1-hydroxy-2-acetonapthanone (3) Schiff base and characterizedviaspectroscopic methods. The ligand was synthesizedviasonication 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 thein vitromammalian chromosome aberration test; in both cases, the samarium complex5was found to be non-mutagenic. The anti-tumor activity of complexes45, and6was assayed against HeLa tumor cells and screened using the MTT assay. The IC50value of complex5was found to be 34 ± 1.2 μg mL−1and this compound exhibited superior activity towards the cells compared to4and6. 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 complex5suggested that the cells underwent the caspase-3-dependent pathway with PARP cleavage. Furthermore, the docking studies of complex5with HSA showed that it was situated in a hydrophilic cavity held by the electrostatic attraction of four hydrogen-bonding interactions. binds with complex5viastrong π-π stacking interactions, which facilitate binding with the major grooves of DNA strands. The above-mentioned results illustrate that for complex5, mitochondrion-mediated apoptosis occursviacaspase-3 activation. Complex5binds with DNAviaintercalation because of S-phase cell cycle arrest in the HeLa cells.

First Page

16457

Last Page

16472

DOI

10.1039/d0ra01936d

Publication Date

4-24-2020

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