The current work investigates the effect of new bifunctional and mononuclear Pt(II) compounds, the cis- and trans-isomers of [PtCl2(NH3)(L)] (L = 1-methyl-7-azaindole, compounds 1 and 2, respectively), on growth and viability of human carcinoma cells as well as their putative mechanism(s) of cytotoxicity. The results show that substitution of 1-methyl-7-azaindole for ammine in cisplatin or transplatin results in an increase of the toxic efficiency, selectivity for tumor cells in cisplatin-resistant cancer cells, and activation of the trans geometry. The differences in the cytotoxic activities of 1 and 2 were suggested to be due to their different DNA binding mode, different capability to induce cell cycle perturbations, and fundamentally different role of transcription factor p53 in their mechanism of action. Interestingly, both isomers make it possible to detect their cellular uptake and distribution in living cells by confocal microscopy without their modification with an optically active tag.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jm501420k | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Co-targeting CDK 4/6 and C-MYC/STAT3/CCND1 axis and inhibition of tumorigenesis and epithelial-mesenchymal-transition in triple negative breast cancer by Pt(II) complexes bearing NH as trans-co-ligand.
J Inorg Biochem
October 2024
Inner Mongolia University Research Center for Glycochemistry of Characteristic Medicinal Resources, Department of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot, People's Republic of China. Electronic address:
In search of potential anticancer agents, we synthesized SNO-donor salicylaldimine main ligand-based Pt(II) complexes bearing NH as co-ligand at trans-position (C1-C6). These complexes showed similarity in structure with transplatin as the two N donor atoms of the main ligand and NH co-ligand were coordinated to Pt in trans position to each other. Each complex with different substituents on the main ligand was characterized thoroughly by detailed spectroscopic and spectrophotometric methods.
View Article and Find Full Text PDFModes of Interactions with DNA/HSA Biomolecules and Comparative Cytotoxic Studies of Newly Synthesized Mononuclear Zinc(II) and Heteronuclear Platinum(II)/Zinc(II) Complexes toward Colorectal Cancer Cells.
Int J Mol Sci
March 2024
Faculty of Medical Sciences, Center for Molecular Medicine and Stem Cell Research, University of Kragujevac, S. Markovića 69, 34000 Kragujevac, Serbia.
A series of mono- and heteronuclear platinum(II) and zinc(II) complexes with 4,4',4″-tri--butyl-2,2':6',2″-terpyridine ligand were synthesized and characterized. The DNA and protein binding properties of [ZnCl(terpy)] (), [{-PtCl(NH)(-pyrazine)ZnCl(terpy)}](ClO) (), [{-PtCl(NH)(-pyrazine)ZnCl(terpy)}](ClO) (), [{-PtCl(NH)(-4,4'-bipyridyl)ZnCl(terpy)}](CIO) () and [{-PtCl(NH)(-4,4'-bipyridyl)ZnCl(terpy)}](CIO) () (where terpy = 4,4',4″-tri--butyl-2,2':6',2″-terpyridine), were investigated by electronic absorption, fluorescence spectroscopic, and molecular docking methods. Complexes featuring transplatin exhibited lower and constant values compared to cisplatin analogs.
View Article and Find Full Text PDFA Transparent and Injectable Biomaterial Prepared by Mixing Collagen and Anti-Cancer Platinum Derivatives.
Macromol Biosci
June 2024
Waseda Research Institute for Science and Engineering, Tokyo, 169-8555, Japan.
This study presents the synthesis of a cross-linked collagen material, named platinum-containing collagen gel (PCG), which is achieved by simply mixing collagen and derivatives of an anti-cancer platinum complex. The cross-linking reagents are derivatives of cisplatin or transplatin, generated through a ligand exchange with dimethyl sulfoxide. PCG exhibits superior physical strength and transparency compared with the native collagen gel formed through spontaneous fibril formation.
View Article and Find Full Text PDFOn the mechanism of action of arsenoplatins: arsenoplatin-1 binding to a B-DNA dodecamer.
Dalton Trans
February 2024
Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, via Cintia, 80126, Naples, Italy.
The reaction of Pt-based anticancer agents with arsenic trioxide affords robust complexes known as arsenoplatins. The prototype of this family of anticancer compounds is arsenoplatin-1 (AP-1) that contains an As(OH) fragment linked to a Pt(II) moiety derived from cisplatin. Crystallographic and spectrometric studies of AP-1 binding to a B-DNA double helix dodecamer are presented here, in comparison with cisplatin and transplatin.
View Article and Find Full Text PDFG-quadruplex inducer/stabilizer pyridostatin targets SUB1 to promote cytotoxicity of a transplatinum complex.
Nucleic Acids Res
April 2022
Beijing National Laboratory for Molecular Sciences; CAS Key Laboratory of Analytical Chemistry for Living Biosystems; National Centre for Mass Spectrometry in Beijing, Institute of Chemistry, Chinese Academy of Sciences, No. 2 Zhongguancun North First Street, Haidian District, 100190 Beijing, P.R. China.
Pyridostatin (PDS) is a well-known G-quadruplex (G4) inducer and stabilizer, yet its target genes have remained unclear. Herein, applying MS proteomics strategy, we revealed PDS significantly downregulated 22 proteins but upregulated 16 proteins in HeLa cancer cells, of which the genes both contain a number of G4 potential sequences, implying that PDS regulation on gene expression is far more complicated than inducing/stabilizing G4 structures. The PDS-downregulated proteins consequently upregulated 6 proteins to activate cyclin and cell cycle regulation, suggesting that PDS itself is not a potential anticancer agent, at least toward HeLa cancer cells.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!