A1 Journal article (refereed)
Oxidative DNA cleavage mediated by a new unexpected [Pd(BAPP)][PdCl4] complex (BAPP = 1,4-bis(3-aminopropyl)piperazine) : crystal structure, DNA binding and cytotoxic behavior (2022)

Ragab, M. S., Shehata, M. R., Shoukry, M. M., Haukka, M., & Ragheb, M. A. (2022). Oxidative DNA cleavage mediated by a new unexpected [Pd(BAPP)][PdCl4] complex (BAPP = 1,4-bis(3-aminopropyl)piperazine) : crystal structure, DNA binding and cytotoxic behavior. RSC Advances, 12(3), 1871-1884. https://doi.org/10.1039/d1ra07793g

JYU authors or editors

Publication details

All authors or editors: Ragab, Mona S.; Shehata, Mohamed R.; Shoukry, Mohamed M.; Haukka, Matti; Ragheb, Mohamed A.

Journal or series: RSC Advances

eISSN: 2046-2069

Publication year: 2022

Volume: 12

Issue number: 3

Pages range: 1871-1884

Publisher: Royal Society of Chemistry (RSC)

Publication country: United Kingdom

Publication language: English

DOI: https://doi.org/10.1039/d1ra07793g

Publication open access: Openly available

Publication channel open access: Open Access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/79409

Abstract

A novel Pd(II) double complex, [Pd(BAPP)][PdCl4], containing the 1,4-bis(3-aminopropyl)piperazine (BAPP) ligand is investigated. X-ray crystallography of a single crystal confirmed the structure of the [Pd(BAPP)][PdCl4] complex. The spectroscopic behavior was also elucidated using elemental analysis, nuclear magnetic resonance and Fourier-transform infrared spectroscopy, and mass spectrometry. The antimicrobial susceptibility of the [Pd(BAPP)][PdCl4] complex against all tested microbial strains was lower than that of the BAPP ligand except for C. albicans. The cytotoxic impacts of the BAPP ligand and its [Pd(BAPP)][PdCl4] complex were evaluated in vitro for HepG2, CaCo-2 and MCF7 cell lines as well as the WI-38 normal cell line. The anticancer activity was markedly improved by the complexation. The [Pd(BAPP)][PdCl4] complex could selectively inhibit the tested cancer cells in a safe way to the non-tumorigenic cell (WI-38). From the DNA binding studies with ultraviolet-visible spectrophotometry, the [Pd(BAPP)][PdCl4] complex interacts more efficiently with the calf thymus DNA than its BAPP ligand through the intercalative binding mode. In the absence of an external reductant, the [Pd(BAPP)][PdCl4] complex cleaved the intact supercoiled pBR322 DNA under physiological conditions in a concentration-dependent manner. Additionally, electrophoretic experiments were performed in the presence of different radical scavengers, namely DMSO, NaN3 and KI, and ruled out the hydrolytic mechanistic pathway of the reaction and suggested that the oxidative mechanism is the preferred one. The results of the binding affinity of the [Pd(BAPP)][PdCl4] complex to human DNA were modeled using a molecular docking study showing that the complex interacts more strongly with human DNA than the ligand. Finally, an in vitro pharmacokinetic study was assessed through in silico ADME predictions.

Keywords: coordination complexes; bioactive compounds; antimicrobial compounds; cytostatic drugs; oxidation-reduction reaction; DNA

Free keywords: crystal structure; DNA binding; cytotoxic behavior

Contributing organizations

Ministry reporting: Yes

Reporting Year: 2022

Preliminary JUFO rating: 1