Palladium(II) complexes bearing thiosemicarbazone and phosphines as inhibitors of DNA-Topoisomerase II enzyme: Synthesis, characterizations and biological studies

Lima, Mauro A.; Costa, Vinicius A.; Franco, Mariane Aralijo; Oliveira, Gabriela P.; Deflon, Victor M.; Rocha, Fábio R.P.

doi:10.1016/j.inoche.2019.107708

Cited by 19 publications

(6 citation statements)

References 30 publications

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“…51 Through noncovalent interactions such as groove and intercalation modes, certain thiosemicarbazone Pd complexes exhibit weak binding to DNA. 52,53 Their cytotoxic effects are not countered by the low preference for DNA. Without preferential DNA binding, other Pd targets, such as topoisomerase I and II, which have a positive correlation with colon cancer, are highly effective at causing cell death.…”

Section: The Dna Fragmentationmentioning

confidence: 99%

Role of the auxiliary ligand in determining the genotoxicity and mode of cell death of thiosemicarbazone Pd(ii) complexes

Mansour,

Khaled,

Radacki

et al. 2024

Dalton Trans.

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Section: The Dna Fragmentationmentioning

confidence: 99%

Role of the auxiliary ligand in determining the genotoxicity and mode of cell death of thiosemicarbazone Pd(ii) complexes

Mansour,

Khaled,

Radacki

et al. 2024

Dalton Trans.

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“…20,21 Furthermore, heterocyclic TSCs generally target intracellular moieties like N-myc downstream-regulated gene-1 (NDRG1) and DNA topoisomerase IIa and ribonucleotide reductase (top2a). 22,23 TSCs show selectivity toward cancer cells, as it has an affinity toward proteins that are excessively expressed in various cancer cells (such as cytochrome P450 [CYPs]), 24 and toward multidrug-resistant cells. 25 Furthermore, polyaromatic hydrocarbons (PAHs) like pyrene-and fluorenebased compounds have shown considerable bioactivities.…”

Section: Introductionmentioning

confidence: 99%

Exploring the anticancer potential of thiadiazole derivatives of substituted thiosemicarbazones formed via copper‐mediated cyclization

Palakkeezhillam

Haribabu

Kumar

et al. 2023

Applied Organom Chemis

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A couple of N‐(4)‐morpholine/pyrrolidine‐substituted thiosemicarbazones (TSCs) of fluorene‐2‐carboxaldehyde (FM and FP), and their corresponding thiadiazoles (TDZs) (CFM and CFP), were synthesized and characterized (elemental analysis, ultraviolet–visible [UV–Visible], Fourier transform infrared [FT‐IR], nuclear magnetic resonance [NMR; 1H & 13C], high‐resolution mass spectrometry [HRMS], and single‐crystal X‐ray diffraction [SCXRD]) for the evaluation of their anticancer potential. The TDZs were obtained unexpectedly and are possibly formed via single‐step metal (copper)‐mediated oxidative cyclizations of the TSCs. The synthesized compounds are fairly stable in phosphate buffer at the biological pH of 7.4. The density functional theory [DFT] studies were performed to predict the optimized structures and physicochemical properties of these compounds. The compounds were further subjected to computational and experimental biomolecular investigations in order to evaluate their anticancer activity in detail. CFM had the most potent activity against human breast adenocarcinoma (MCF‐7) and human urinary bladder (T24) cancer cells, with IC50 values of 12.00 and 24.80 μM, respectively. In contrast, CFM had negligible cytotoxicity (IC50 = 98.70 μM) against kidney epithelial cells extracted from an African green monkey (Vero) normal cells. This outcome was preferable to that of the widely used medicine Cisplatin. Molecular docking studies were performed with the breast cancer protein “cytochrome P450 1A1” (CYP1A1) and bovine serum albumin (BSA) to predict how effectively the compounds bind to the receptor. The ADMET findings suggest that these compounds have considerable drug‐likeness and oral bioavailability. These insights may open the door for additional medical research into the bioactivities of TSCs and TDZs produced from bioactive carbonyl compounds.

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“…There has been a growing interest in expanding the anticancer activity of metallo-compounds besides Pt-drugs. Among the non-Pt-drugs, Pd(II) complexes have become promising alternatives by displaying better anti-proliferative properties and favourable toxicity profile [1][2][3][4]. Pd(II) complexes have been viewed as suitable anticancer drug candidates due their noticeable enzymatic catalytic attributes and ability to cleave the double structure of DNA [3].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, substitution kinetics, DNA/BSA binding and cytotoxicity of tridentate N^E^N (E = NH, O, S) pyrazolyl palladium(II) complexes

Omondi

Fadaka²,

Fatokun³

et al. 2022

J Biol Inorg Chem

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The pincer complexes, [Pd(L 1 )Cl]BF 4 (PdL 1 ), [Pd(L 2 )Cl]BF 4 (PdL 2 ), [Pd(L 3 )Cl]BF 4 (PdL 3 ), [Pd(L 4 )Cl]BF 4 (PdL 4 ) were prepared by reacting the corresponding ligands, 2,6-bis[(1H-pyrazol-1-yl)methyl]pyridine (L 1 ), bis[2-(1H-pyrazol-1-yl)ethyl] amine (L 2 ), bis[2-(1H-pyrazol-1-yl)ethyl]ether (L 3 ), and bis[2-(1H-prazol-1-yl)ethyl]sulphide (L 4 ) with [PdCl 2 (NCMe)] 2 in the presence NaBF 4 . The solid-state structures of complexes PdL 1 -PdL 4 confirmed a tridentate coordination mode,with one chloro ligand completing the coordination sphere to afford square-planar complexes. Chemical behaviour of the complexes in solution confirms their stability in both aqueous and DMSO stock media. The electrochemical properties of the compounds showed irreversible two-electron reduction process. Kinetic reactivity of Pd complexes with the biological nucleophiles viz, thiourea (Tu), L-methionine (L-Met) and guanosine 5′-diphosphate disodium salt (5'-GMP) followed the order: PdL 2 < PdL 3 < PdL 4 , and PdL 2 < PdL 1 . The kinetic reactivity is subject to the electronic effects of the spectator ligand(s), and the trend was supported by the DFT computed results. The palladium complexes PdL 1 -PdL 4 bind to calf thymus (CT-DNA) via intercalation mode. In addition, the bovine serum albumin (BSA) showed good binding affinity to the complexes. The mode of quenching mechanism of the intrinsic fluorescence of CT-DNA and BSA by the complexes was found to be static. The order of interactions of the complexes with DNA and BSA was in tandem with the rate of substitution kinetics. The complexes, however, displayed relatively low cytotoxicity (IC 50 > 100 µM) when tested against the human cervical adenocarcinoma (HeLa) cell line and the transformed human lung fibroblast cell line (MRC-5 SV2).

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Palladium(II) complexes bearing thiosemicarbazone and phosphines as inhibitors of DNA-Topoisomerase II enzyme: Synthesis, characterizations and biological studies

Cited by 19 publications

References 30 publications

Role of the auxiliary ligand in determining the genotoxicity and mode of cell death of thiosemicarbazone Pd(ii) complexes

Role of the auxiliary ligand in determining the genotoxicity and mode of cell death of thiosemicarbazone Pd(ii) complexes

Exploring the anticancer potential of thiadiazole derivatives of substituted thiosemicarbazones formed via copper‐mediated cyclization

Synthesis, substitution kinetics, DNA/BSA binding and cytotoxicity of tridentate N^E^N (E = NH, O, S) pyrazolyl palladium(II) complexes

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