Interaction with CT-DNA and in vitro cytotoxicity of two new copper(II)-based potential drugs derived from octanoic hydrazide ligands

• Published in: Journal of inorganic biochemistry Vol. 256; p. 112546
• Main Authors: Chowdhury, Manas, Biswas, Niladri, Saha, Sandeepta, Rahaman, Ashikur, Gupta, Poulami Sen, Banerjee, Ankur, Mandal, Deba Prasad, Bhattacharjee, Shamee, Zangrando, Ennio, Sciortino, Giuseppe, Pisanu, Federico, Garribba, Eugenio, Roy Choudhury, Ruma, Roy Choudhury, Chirantan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2024
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Computational calculations; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Copper - chemistry; Copper(II) complexes; Cytotoxicity; DNA - chemistry; DNA binding; EPR; Humans; Hydrazines - chemistry; Hydrazines - pharmacology; Hydrazones - chemical synthesis; Hydrazones - chemistry; Hydrazones - pharmacology; Ligands; Molecular Docking Simulation; Pyridines - chemistry; Pyridines - pharmacology; X-ray structure; Cytotoxicity; Computational calculations; Copper(II) complexes; X-ray structure; EPR; DNA binding
• ISSN: 0162-0134; 1873-3344; 1873-3344
• DOI: 10.1016/j.jinorgbio.2024.112546

Two copper(II) complexes [Cu(Hpmoh)(NO3)(NCS)] (1) and [Cu(peoh)(N3)]2 (2) were designed and synthesized by reaction of Cu(NO3)2·3H2O with hydrazone Schiff base ligands,abbreviated with Hpmoh and Hpeoh. Hpmoh and Hpeoh were prepared by condensation reaction of octanoic hydrazide with pyridine-2-carboxyaldehyde and 2-acetylpyridine, respectively. Complexes 1 and 2 were characterized using different analytical techniques such as FT-IR, UV–Vis, IR, EPR and single X-ray diffraction (XRD) analyses as well as computational methods (DFT). The XRD of 1 and 2 shows a mononuclear or a dinuclear structure with the copper(II) centre adopting a slightly distorted square pyramidal geometry. In water-containing solution and in DMSO, 1 and 2 undergo a partial transformation with formation of [Cu(Hpmoh)(NO3)(NCS)] (1) and [Cu(Hpmoh)(NO3)(H2O/DMSO)] (1a) in one system and [Cu(peoh)(N3)] (2a) in the other one, as supported by DFT calculations. Docking simulations confirmed that the intercalation is the preferred binding mode with DNA for 1, 1a and 2a, but suggested that the minor groove binding is also possible. A significant fluorescence quenching of the DNA–ethidium bromide conjugate was observed upon the addition of complexes 1 and 2 with a quenching constant around 104 M−1 s−1. Finally, both 1 and 2 were examined for anti-cancer activity using MDA-MB-231 (human breast adenocarcinoma) and A375 (malignant melanoma) cell lines through in vitro MTT assay which suggest comparable cancer cell killing efficacy, with the higher effectiveness of 2 due to the dissociation into two [Cu(peoh)(N3)] units. The synthesis and characterization of two new mononuclear and dinuclear copper(II) complexes with hydrazone Schiff base ligands were reported. Both of them bind to calf thymus-DNA with an intercalative binding and show high cytotoxicity against MDA-MB-231 (human breast adenocarcinoma) and A375 (malignant melanoma) cell lines. [Display omitted] •Two copper(II) complexes with hydrazone Schiff base ligands were studied.•One mononuclear and one dinuclear Cu(II) species were characterized.•Dinuclear complex dissociate into two monomeric Cu(II) moieties in solution.•Both the complexes show interaction with CT-DNA.•Both the complexes are active against MDA-MB-231 and A375 cell lines.