ArticleMetallomics : integrated biometal science2012
Analysis of the DNA damage produced by a platinum-acridine antitumor agent and its effects in NCI-H460 lung cancer cells.
Article in Metallomics : integrated biometal science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- An Overview of Acridine Analogs: Pharmacological Significance and Recent Developments.Current medicinal chemistry · 2025Review
- Quantifying Intracellular Platinum Accumulation Using Inductively Coupled Mass Spectrometry.Current protocols · 2024Article
- Potential of covalently linked tamoxifen hybrids for cancer treatment: recent update.RSC medicinal chemistry · 2024Review
- Acridine as an Anti-Tumour Agent: A Critical Review.Molecules (Basel, Switzerland) · 2022Review
- DNA Adduct Detection after Post-Labeling Technique with PCR Amplification (DNA-ADAPT-qPCR) Identifies the Pre-ribosomal RNA Gene as a Direct Target of Platinum-Acridine Anticancer Agents.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Evaluation of a Platinum-Acridine Anticancer Agent and Its Liposomal Formulation in an in vivo Model of Lung Adenocarcinoma.ChemMedChem · 2021Article
- A membrane transporter determines the spectrum of activity of a potent platinum-acridine hybrid anticancer agent.Scientific reports · 2020Article
- Large-Pore Functionalized Mesoporous Silica Nanoparticles as Drug Delivery Vector for a Highly Cytotoxic Hybrid Platinum-Acridine Anticancer Agent.Chemistry (Weinheim an der Bergstrasse, Germany) · 2017Article
- Design and cellular studies of a carbon nanotube-based delivery system for a hybrid platinum-acridine anticancer agent.Journal of inorganic biochemistry · 2016Article
- Cellular Recognition and Repair of Monofunctional-Intercalative Platinum--DNA Adducts.Chemical research in toxicology · 2015Article
- Design of enzymatically cleavable prodrugs of a potent platinum-containing anticancer agent.Chemistry (Weinheim an der Bergstrasse, Germany) · 2014Article
- Redesigning the DNA-targeted chromophore in platinum-acridine anticancer agents: a structure-activity relationship study.Chemistry (Weinheim an der Bergstrasse, Germany) · 2014Article
- Synthetic methods for the preparation of platinum anticancer complexes.Chemical reviews · 2014Review
- Investigating the cellular fate of a DNA-targeted platinum-based anticancer agent by orthogonal double-click chemistry.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2014Article
- Design of a platinum-acridine-endoxifen conjugate targeted at hormone-dependent breast cancer.Chemical communications (Cambridge, England) · 2013Article
- Using fluorescent post-labeling to probe the subcellular localization of DNA-targeted platinum anticancer agents.Angewandte Chemie (International ed. in English) · 2013Article
- Using a build-and-click approach for producing structural and functional diversity in DNA-targeted hybrid anticancer agents.Journal of medicinal chemistry · 2012Article
- Synthesis, aqueous reactivity, and biological evaluation of carboxylic acid ester-functionalized platinum-acridine hybrid anticancer agents.Journal of medicinal chemistry · 2012Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
High-performance liquid chromatography in conjunction with electrospray mass spectrometry (LC-ESMS) was used to structurally characterize the adducts formed by the platinum-acridine agent [PtCl(en)(N-(2-(acridin-9-ylamino)ethyl)-N-methylpropionimidamide)](NO(3))(2) (compound 1) in cell-free DNA. Compound 1 forms monofunctional adducts exclusively with guanine, based on the fragments identified in enzymatic digests (dG*, dGMP*, dApG*, and dTpG*, where the asterisk denotes bound drug). The time course of accumulation and DNA adduct formation of compound 1 and the clinical drug cisplatin in NCI-H460 lung cancer cells at physiologically relevant drug concentrations (0.1 μM) was studied by inductively-coupled plasma mass spectrometry (ICP-MS). Compound 1 accumulates rapidly in cells and reaches intracellular levels of up to 60-fold higher than those determined for cisplatin. The hybrid agent shows unusually high DNA binding levels: while cisplatin adducts form at a maximum frequency of 5 adducts per 10(6) nucleotides, compound 1 produces 25 adducts per 10(6) nucleotides after only 3 h of continuous incubation with the lung cancer cells. The high overall levels of compound 1 in the cells and in cellular DNA over the entire 12-h treatment period translate into a rapid decrease in cell viability. Possible implications of these findings for the mechanism of action of compound 1 and the agent's potential to overcome tumor resistance to cisplatin are discussed.
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