Newly synthesised Schiff base metal complexes, characterisation, and contribution as enhancers of colon cancer cell apoptosis by overexpression of P53 protein

Abstract

Fluoroquinolones emerged as one of potent therapeutic agents, targeting DNA‐signalling pathways. Thus, efforts were spent to create novel quinolones for optimizing their antimicrobial and anticancer properties. Therefore, the new compound N , N ′‐phenylene (bis1‐cyclopropyl‐7‐(4‐ethylpiperazin‐1‐yl)‐6‐fluoro‐1,4‐dihydroquinoline‐3‐carboxylic acid) (H 2 Enro‐o‐phdn) in addition to its related chelates‐contained metals were synthesised and described by spectroscopic, physical methods and thermal analyses. The reaction between H 2 Enro‐o‐phdn and trivalent La(III), Y(III), and Fe(III) and tetravalent Zr(IV) chloride with molar ratio 1:1 (M:H 2 Enro‐o‐phdn) yielded the production of chelates. The infrared results elucidate the binding mode of H 2 Enro‐o‐phdn by means of azomethine nitrogen and carboxylato oxygen atoms as tetradentate. The thermal analyses assured the proposed formula as well as existence of coordinated and latticed H 2 O molecules. Kinetic parameters for investigated metal complexes were quantified utilisation Horowitz–Metzger in addition to Coats–Redfern methods. Regarding antibacterial efficacy, Y(III) and Fe(III) complexes showed a robust inhibitory activity towards negative‐gram stained ( Escherichia coli and Salmonella typhi ) and positive‐Gram stained ( Staphylococcus aureus and “spore‐forming” Bacillus cereus ) strains. Then, we further tested the cytotoxicity of the complexes against the survival of colon‐cancer cells line (CT26). In this regard, in the descending order, Fe(III) > Zr(IV) > La(III) complexes possessed a powerful antitumour activity with IC 50 values 6.38, 5.36, and 4.03 μM, respectively, compared with the anticancer drug‐reference cisplatin (16.77 μM). To understand the precise mechanism behind the tumour cell death, Western‐blotting analysis was conducted, to monitor the changes in levels of pro‐apoptotic “P53” protein after drug‐treatment. Results indicated that H 2 Enro‐o‐phdn with higher covalency metals, like La(III) and Zr(IV) complexes, had the highest upregulation of P53 expression in a threefold to fourfold compared cisplatin, paving the way for a novel P53‐based colon‐cancer therapies.