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

Manas Chowdhury, Niladri Biswas, Sandeepta Saha, Ashikur Rahaman, Poulami Sen Gupta, Ankur Banerjee, Deba Prasad Mandal, Shamee Bhattacharjee, Ennio Zangrando, Giuseppe Sciortino, Federico Pisanu, Eugenio Garribba, Ruma Roy Choudhury, Chirantan Roy Choudhury

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number112546
JournalJournal of Inorganic Biochemistry
Volume256
DOIs
StatePublished - Jul 2024
Externally publishedYes

Keywords

  • Computational calculations
  • Copper(II) complexes
  • Cytotoxicity
  • DNA binding
  • EPR
  • X-ray structure

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